Type 2 Diabetes in Adults

Type 2 diabetes
in adults
Straight to the point of care
Last updated: Feb 22, 2022

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 4
Case history 5
Diagnosis 6
Approach 6
History and exam 9
Risk factors 11
Investigations 12
Differentials 15
Criteria 17
Screening 18
Management 19
Approach 19
Treatment algorithm overview 40
Treatment algorithm 43
Primary prevention 94
Secondary prevention 95
Patient discussions 95
Follow up 97
Monitoring 97
Complications 99
Prognosis 102
Guidelines 103
Diagnostic guidelines 103
Treatment guidelines 105
Online resources 108
Evidence tables 109
References 113
Images 137
Disclaimer 138
Type 2 diabetes in adults Overview
Summary
Type 2 diabetes should be managed with a personalised self-management programme, with a focus on diet
and lifestyle interventions.
OVERVIEW
Glycaemic goals and treatment choices should be individualised. Initial antihyperglycaemic therapy is with
metformin, although sodium-glucose co-transporter-2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1)
agonists are increasingly preferred for high-risk patients because of their cardiovascular and renal benefits.
Dual therapy, triple therapy, and/or insulin may be needed to achieve good glycaemic control.
Selected glucose-lowering drugs reduce all-cause and cardiovascular mortality.
Blood pressure control, lipid management, smoking cessation, and glycaemic management reduce the risk
of macrovascular complications such as heart attack and stroke. Glycaemic control and blood pressure
management reduce the risk of microvascular complications (neuropathy, nephropathy, retinopathy).
Definition
Type 2 diabetes mellitus is a progressive disorder defined by deficits in insulin secretion and increased
insulin resistance that lead to abnormal glucose metabolism and related metabolic derangements.[1]
Although the aetiologies of type 1 and type 2 diabetes differ dramatically, both lead to hyperglycaemic states,
and both share common macrovascular (coronary heart, cerebrovascular, and peripheral vascular disease)
and microvascular (retinopathy, nephropathy, and neuropathy) complications.
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Type 2 diabetes in adults Theory
Epidemiology
Diabetes prevalence is increasing worldwide, compounded by population growth and an ageing
population.[2] [3] In 1980, the global age-standardised diabetes prevalence was 4.3%.[2] In 2019, the
THEORY
global age-standardised diabetes prevalence was estimated at 8.3%.[4] Survey data of diabetes in adults
does not separate type 1 and type 2 diabetes, but most cases of diabetes (around 90%) are type 2.[2] In
most countries, the incidence of diagnosed diabetes rose from the 1990s to the mid-2000s, but has been
plateauing since.[3] It is thought that this downward trend might be owing to public health education and
preventive strategies. Data are limited in developing countries and the trend in these regions might differ.[3]
Clinical onset is usually preceded by many years of insulin resistance and hyperinsulinaemia before elevated
glucose levels are detectable.[1]
Patients with type 2 diabetes have a very high risk of concurrent hypertension (80% to 90%), lipid disorders
(70% to 80%), and overweight or obesity (60% to 70%).[5] When diabetes is diagnosed at age 40 years,
men lose an average of 5.8 years of life, and women lose an average of 6.8 years of life, highlighting the
importance of primary prevention of diabetes.[6] However, onset of diabetes at older ages has much less
effect on life expectancy if acceptable glucose, blood pressure, and lipid control can be achieved and
maintained.
Aetiology
Type 2 diabetes often presents on a background genetic predisposition and is characterised by insulin
resistance and relative insulin deficiency. Insulin resistance is aggravated by ageing, being overweight (body
mass index [BMI] 25.0 to 29.9 kg/m²), and obesity (BMI >30 kg/m²) in particular. Among obese patients,
weight loss often reduces the degree of insulin resistance and may delay diabetes onset or ameliorate
diabetes severity and thereby reduce risk of long-term complications. Insulin resistance affects primarily
the liver, muscle, and adipocytes, and it is characterised by complex derangements in cellular receptors,
intracellular glucose kinase function, and other intracellular metabolic processes.[7] The complexity and
variety of these intracellular derangements suggest that what is now classified as type 2 diabetes may be in
fact a larger group of conditions that await future definition.
Pathophysiology
The precise mechanism by which the diabetic metabolic state leads to microvascular and macrovascular
complications is only partly understood but probably involves both uncontrolled blood pressure (BP)
and uncontrolled glucose, increasing the risk of microvascular complications such as retinopathy and
nephropathy. Mechanisms may involve defects in aldose reductase and other metabolic pathways,
damage to tissues from accumulation of glycated end products, and other mechanisms. With respect to
macrovascular complications, high BP and glucose raise risk, but so do lipid abnormalities and tobacco
use. One unifying theory postulates the existence of a metabolic syndrome that includes diabetes mellitus,
hypertension, dyslipidaemias, and obesity, and predisposes to coronary heart disease, stroke, and peripheral
artery disease.[7] [8] However, this theory is not universally accepted as more clinically useful than assessing
individual cardiovascular risk factors.[9]
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 22, 2022.
Type 2 diabetes in adults Theory
Case history
Case history #1
THEORY
An overweight 55-year-old woman presents for preventative care. She notes that her mother died of
diabetes, but reports no polyuria, polydipsia, or weight loss. BP is 144/92 mmHg, fasting blood sugar
8.2 mmol/L (148 mg/dL), HbA1c 65 mmol/mol (8.1%), LDL-cholesterol 5.18 mmol/L (200 mg/dL), HDL-
cholesterol 0.8 mmol/L (30 mg/dL), and triglycerides 6.53 mmol/L (252 mg/dL).
Other presentations
Patients with type 2 diabetes can also present with symptoms such as blurred vision; fatigue; erectile
dysfunction; urinary tract or candidal infections; dry itchy skin; paresthaesias; increased urination, thirst,
and appetite; or unexplained weight loss.
5
Type 2 diabetes in adults Diagnosis
Approach
Type 2 diabetes is most often diagnosed on routine screening.
Strong risk factors, which also indicate the need for screening, include: older age; overweight/obesity; certain
ethnic groups (including black, South Asian, or Hispanic ancestry); family history of type 2 diabetes; history
of gestational diabetes; presence of non-diabetic hyperglycaemia; polycystic ovary syndrome; hypertension;
dyslipidaemia; or known cardiovascular disease.[11] [15]
Symptomatic patients may present with: fatigue; polyuria, polydipsia, polyphagia, or weight loss (usually
when hyperglycaemia is more severe [e.g., >16.6 mmol/L, >300 mg/dL]); blurred vision; paraesthesias; skin
infections (bacterial or candidal); urinary tract infections; or acanthosis nigricans.
DIAGNOSIS
Acanthosis nigricans involving the axilla

From the collection of Melvin Chiu, MD; used with permission
The presence of symptoms may indicate more overt hyperglycaemia.
Diagnosis
Use the World Health Organization criteria to establish a firm diagnosis of diabetes in a non-pregnant
adult:[44]
• Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL), or

• Plasma glucose ≥11.1 mmol/L (≥200 mg/dL) 2 hours after 75 g oral glucose, or
• Glycosylated haemoglobin (HbA1c) ≥48 mmol/mol (≥6.5%), or
• In a symptomatic patient, random plasma glucose of ≥11.1 mmol/L (≥200 mg/dL).
Do not diagnose diabetes in an asymptomatic person based on a single test result.
• A repeat confirmatory test on a subsequent day is required in asymptomatic patients.[45]

• In practice, a patient with severe symptoms and elevated test results does not usually need a
repeat test.
Check urine ketones at diagnosis if the patient is symptomatic of hyperglycaemia (polyuria, polydipsia,
weakness) and volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension,
and, in severe cases, shock). Continue to monitor throughout the course of disease.
• If increased ketone levels are left untreated, they can lead to progressive dehydration and diabetic
ketoacidosis (DKA). DKA is a severe, life-threatening complication of diabetes. More commonly
seen in patients with type 1 diabetes, DKA may also occur in patients with type 2 diabetes,
particularly:[46] [47] [48] [49]
• In the presence of an underlying infection or other stressors

• Following cardiovascular events, malignancy, antipsychotic medication, and concomitant
treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors.
• See our topic 'Diabetic ketoacidosis'.
Some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of
diagnosis.[15] [44]
DIAGNOSIS
• At initial diagnosis of diabetes, it is important to determine whether immediate treatment with insulin
is required. Type 1 diabetes can occur at any age but tends to be diagnosed in younger (age <35
years), thinner patients, and has a more rapid onset and often more severe symptoms than type 2
diabetes.
• Do not routinely measure C-peptide and/or diabetes-specific autoantibody titres at initial
presentation to distinguish type 2 diabetes from type 1 diabetes. The National Institute for Health
and Care Excellence (NICE) in the UK recommends only considering measuring C-peptide if there
is difficulty distinguishing type 1 diabetes from other types.[50]
• If C-peptide testing is indicated, bear in mind that it has better discriminative value the longer
the test is done after initial presentation.[50]
• In clinical practice, C-peptide testing should only be done with a paired glucose. In practical
terms, this can be achieved by using C-peptide on a single non-fasting random blood or urine
sample after the patient has eaten one of their own meals.[51] Otherwise, C-peptide might
be suppressed, making a false positive result more likely. This is a particular concern if the
patient has been started on therapy that can cause hypoglycaemia (e.g., insulin).
7
• If the patient has persistently/significantly raised HbA1c despite oral medication or has
persistent osmotic symptoms/weight loss, consider testing for autoimmunity to help identify
immune-mediated diabetes, the most prevalent form of type 1 diabetes. The patient may
have been wrongly diagnosed with type 2 diabetes.
• Autoantibodies to glutamic acid decarboxylase 65 (GAD), islet cell antibodies (ICA),

insulin antibodies, antibodies to tyrosine phosphatase-related islet antigen-2 (IA-2 and
IA-2beta), and zinc-transporter-8 antibodies (ZnT8) can help to identify individuals with
immune-mediated diabetes, although these antibodies fade with time after onset of
illness.[15] [52] [53] [54]
Evaluation of disease and risks of macrovascular/microvascular

complications
Assess the patient’s blood pressure, smoking status, fasting lipid levels, and liver function tests.
Take baseline urine albumin/creatinine ratio and serum creatinine with estimated glomerular filtration rate
readings, because signs of chronic kidney disease may be present at diagnosis.[15]
Consider clinical assessment of cardiac, carotid, and peripheral circulation, with ECG and vascular
investigation (e.g., an ankle-brachial pressure index) at diagnosis.[42]
Initial and ongoing monitoring

See the 'Monitoring' section of this topic for more detail on ongoing monitoring.
On diagnosis:
• Immediately refer the patient to the local eye screening service[55]

• Assess the patient’s risk of developing a diabetic foot problem; also do this at least annually
thereafter and whenever any foot problems arise[56]
DIAGNOSIS
• Measure the patient’s urine albumin to creatinine ratio and continue to check this every year.
Measure HbA1c levels at diagnosis and:[55]
• Every 3 to 6 months (tailored to individual needs), until the patient’s HbA1c is stable on unchanging
therapy
• Every 6 months once the patient’s HbA1c level and blood glucose-lowering therapy are stable.
Measure blood pressure at least once a year in any adult with type 2 diabetes without previously
diagnosed hypertension or renal disease.[57]
• Offer and reinforce preventive lifestyle advice.[57]

Ensure the patient receives ongoing individualised nutritional advice from a healthcare professional with
specific expertise in nutrition.[55]
Aim to include a routine assessment of frailty in reviews for older people with diabetes.[58] [59] [60] Use
a validated tool (e.g., the electronic Frailty Index [eFI], the Rockwood frailty score, or Timed Up and Go)
to confirm clinical suspicion of frailty.[59] [60] Frail patients need a tailored approach to management;
consult a specialist if you need guidance.
History and exam

Key diagnostic factors
presence of risk factors (common)
• Key risk factors include older age; overweight/obesity; certain ethnic groups (including black, South
Asian, or Hispanic ancestry); family history of type 2 diabetes; history of gestational diabetes;
presence of non-diabetic hyperglycaemia; polycystic ovary syndrome; hypertension; dyslipidaemia; or
known cardiovascular disease.[11] [15]
• One unifying theory postulates the existence of a metabolic syndrome that includes diabetes mellitus,
hypertension, dyslipidaemias, and obesity, and predisposes to coronary heart disease, stroke, and
peripheral artery disease.[8] [61] However, this theory is not universally accepted as more clinically
useful than assessing individual cardiovascular risk factors.[62]
asymptomatic (common)
• It is very common for type 2 diabetes to be asymptomatic and detected on screening. Symptoms,
when present, may indicate more overt hyperglycaemia.
polydipsia (uncommon)
• Usually in patients with fasting plasma glucose >16.6 mmol/L (>300 mg/dL) and/or HbA1c >95 mmol/
mol (>11%). As polydipsia occurs when there is considerable hyperglycaemia, it is rarely seen in
patients with type 2 diabetes (and is a more common presentation in people with type 1 diabetes).
polyuria (uncommon)
mol (>11%). As polyuria occurs when there is considerable hyperglycaemia, it is rarely seen in patients
with type 2 diabetes (and is a more common presentation in people with type 1 diabetes).
Other diagnostic factors
DIAGNOSIS
candidal infections (common)
• Most commonly vaginal, penile, or in skin folds.
skin infections (common)

• Cellulitis or abscesses.
urinary tract infections (common)

• Cystitis or pyelonephritis.
fatigue (common)
• Increased fatigability may be an early warning sign of progressive cardiovascular disease; clinicians
should have a low threshold for cardiac evaluation.
blurred vision (common)

• Due to elevated glucose.
9
polyphagia (uncommon)
mol (>11%).
unintentional weight loss (uncommon)

• If marked hyperglycaemia is present.
paraesthesias (uncommon)
• May occur in the extremities as a result of neuropathy in those with prolonged undiagnosed diabetes.
acanthosis nigricans (uncommon)

• A velvety, light brown-to-black marking, usually on the neck, under the arms, or in the groin. Can occur
at any age. Most often associated with obesity.
DIAGNOSIS
Acanthosis nigricans involving the axilla

Risk factors
Strong
older age
• Older patients are at increased risk. However, the incidence of type 2 diabetes in children and
adolescents is increasing.[10]
overweight/obesity
• Appears to be the precipitating factor leading to clinical expression of diabetes.[11] The mean body
mass index (BMI) at the time of diagnosis of diabetes in several studies is around 31 kg/m², and there
is a graded increase in risk of diabetes with increasing BMI.[12] Clinical trials have shown that weight
loss is associated with delayed or decreased onset of diabetes in high-risk adults.[13]
gestational diabetes
• About 50% of women who have gestational diabetes mellitus will go on to develop overt diabetes
mellitus within 10 years of delivery.[14]
non-diabetic hyperglycaemia
• Non-diabetic hyperglycaemia (sometimes termed pre-diabetes) is major risk factor for onset of type 2
diabetes.[1] [15]
family history of type 2 diabetes

• Although the specific genetic profile that confers risk has yet to be fully elucidated, epidemiological
observations leave little doubt of a substantial genetic component.[7]
non-white ancestry
• Prevalence of diabetes varies by ethnic group. In the UK, type 2 diabetes is more common in people
of African, African-Caribbean, and South Asian family origin.[16] South Asian and East Asian
people are at increased risk of developing type 2 diabetes, probably due to an interplay of diet,
DIAGNOSIS
lifestyle, and genetic factors.[17] [18] [19] [20] Different prevalence rates have been observed for
European Americans, Hispanic Americans, and African-Americans, with people of African, Hispanic, or
American-Indian ancestry at higher risk of diabetes compared with white people.[21] [22]
polycystic ovary syndrome

• Elevated risk; should be periodically screened for diabetes.[11] [15]
hypertension
• Often associated with type 2 diabetes. Periodic screening is recommended in people with essential
hypertension due to increased prevalence of diabetes.[11] [15]
dyslipidaemia
• Especially with low high-density lipoprotein (HDL) and/or high triglycerides: periodic diabetes
screening is recommended due to the high prevalence of diabetes in patients with dyslipidaemia.[15]
11
cardiovascular disease
• Periodic diabetes screening is recommended due to the high prevalence of diabetes in patients with
peripheral vascular and coronary artery disease.[11] [15]
stress
• Stress provokes release of hormones that elevate glucose, and there is some evidence that life stress
may predispose to onset of type 2 diabetes.[23]
Investigations
1st test to order
Test Result
fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL)
• Order after a minimum 8-hour fast. Bear in mind that a repeat
confirmatory test is required for diagnosis in most cases.
HbA1c ≥48 mmol/mol (≥6.5%)
• Reflects degree of hyperglycaemia over the preceding 3 months.
• Bear in mind that a repeat confirmatory test is required for diagnosis
in most cases.
• HbA1c is also used to monitor glycaemic control.
2-hour post-load glucose after 75 g oral glucose ≥11.1 mmol/L (≥200 mg/dL)
• Plasma glucose is measured 2 hours after 75 g oral glucose load.
• Bear in mind that a repeat confirmatory test is required for diagnosis
in most cases.
random plasma glucose ≥11.1 mmol/L (≥200 mg/dL)
• Non-fasting test. Bear in mind that a repeat confirmatory test is
required for diagnosis in most cases.
• Used for rapid assessment of glucose status if symptoms such as
DIAGNOSIS
polyuria, polydipsia, or weight loss are present.
Other tests to consider
Test Result
fasting lipid profile may show high LDL,
low HDL, and/or high
• Dyslipidaemia is common in type 2 diabetes.
triglycerides
urine ketones positive in instances of

ketoacidosis
• Check urine ketones at diagnosis if the patient is symptomatic
of hyperglycaemia (polyuria, polydipsia, weakness) and volume
depletion (dry mucous membranes, poor skin turgor, tachycardia,
hypotension, and, in severe cases, shock). Continue to monitor
throughout the course of disease.
• If increased ketone levels are left untreated, they can lead to
progressive dehydration and diabetic ketoacidosis (DKA). DKA is a
severe, life-threatening complication of diabetes. More commonly
seen in patients with type 1 diabetes, DKA may also occur in patients
with type 2 diabetes, particularly in the presence of an underlying
infection (or other stressors) or following cardiovascular events,
malignancy, antipsychotic medication, and concomitant treatment
with sodium-glucose co-transporter-2 (SGLT2) inhibitors.[46] [47] [48]
• See our topic 'Diabetic ketoacidosis'.
albumin to creatinine ratio (ACR) may be increased; ACR
≥3 mg/mmol indicates
• Indicates nephropathy and suggests possible other microvascular
clinically important
damage.
proteinuria[63]
• Monitored yearly.
• May be assessed with a random urine sample.[15]
serum creatinine and estimated GFR may show renal
insufficiency
• GFR is calculated according to the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) or Modification of Diet in
Renal Disease (MDRD) formulas. The CKD-EPI formula is now
recommended by the Kidney Disease Outcomes Quality Initiative
(KDOQI) because it removes bias at higher GFR levels, allowing for
DIAGNOSIS
reporting across a full range.
ECG may indicate prior
ischaemia
• Baseline assessment. A normal ECG does not rule out coronary
artery disease. Patients with an abnormal resting ECG may require
further cardiac investigation.[15]
ankle-brachial pressure index (ABPI) ≤0.9 is abnormal
• A non-invasive tool to detect peripheral arterial disease (PAD), which
has a high prevalence in patients with diabetes. The National Institute
for Health and Care Excellence in the UK recommends that ABPI
should be performed in patients with suspected PAD.[64]
• Due to the potential for calcification of the arteries from
atherosclerotic peripheral vascular disease (which falsely elevates
the ankle-brachial index), toe pressure testing is often done as an
adjunct to ABPI testing. A normal ABPI value is 1.0; a normal toe
pressure value is 0.7. Do not exclude a diagnosis of PAD in people
with diabetes based on a normal or raised ABPI.[64]
random C-peptide normal or high
• Do not routinely measure C-peptide at initial presentation to
distinguish type 2 diabetes from type 1 diabetes. The National
13
Test Result
Institute for Health and Care Excellence in the UK recommends only
considering measuring C-peptide if there is difficulty distinguishing
type 1 diabetes from other types.[50]
• If C-peptide testing is indicated, bear in mind that it has better
discriminative value the longer the test is done after initial
presentation.[50]
• In clinical practice, C-peptide testing should only be done with a
paired glucose. In practical terms, this can be achieved by using C-
peptide on a single non-fasting random blood or urine sample after
the patient has eaten one of their own meals.[51] Otherwise, C-
peptide might be suppressed, making a false positive result more
likely. This is a particular concern if the patient has been started on
therapy that can cause hypoglycaemia (e.g., insulin).
autoantibody testing negative
• Do not routinely measure diabetes-specific autoantibody titres
at initial presentation to distinguish type 2 diabetes from type 1
diabetes.[50] If the patient has persistently/significantly raised HbA1c
despite oral medication or persistent osmotic symptoms/weight loss,
consider testing for autoimmunity to help identify immune-mediated
diabetes, the most prevalent form of type 1 diabetes. The patient may
have been wrongly diagnosed with type 2 diabetes.
• Autoantibodies to glutamic acid decarboxylase 65 (GAD), islet
cell antibodies (ICA), insulin antibodies, antibodies to tyrosine
phosphatase-related islet antigen-2 (IA-2 and IA-2beta), and zinc-
transporter-8 antibodies (ZnT8) can help to identify individuals with
immune-mediated diabetes, although these antibodies fade with time
after onset of illness.[15] [52] [53] [54]
liver function tests may be elevated
• May identify people with non-alcoholic fatty liver disease (NAFLD).
The prevalence of NAFLD in people with type 2 diabetes is thought to
be 40% to 70%.[65]
DIAGNOSIS
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Non-diabetic • Patients with non-diabetic • NDH is defined as raised
hyperglycaemia (pre- hyperglycaemia (NDH) blood glucose levels (HbA1c
diabetes) often have no specific 42 to 47 mmol/mol [6.0%
differentiating signs or to 6.4%]; or fasting glucose
symptoms as both NDH and 5.5 to 6.9 mmol/L [99.0 to
type 2 diabetes are generally 124.2 mg/dL]) that are not
asymptomatic. in the diabetic range but are
associated with an increased
risk of developing type 2
diabetes.[26]
Diabetes mellitus, type 1 • Tends to present in • Urine ketones are often

childhood or adolescence present in type 1 diabetes,
with the highest incidence but may be positive in type
observed in children aged 10 2 diabetes if there is severe
to 14 years, but can occur at volume depletion.
any age.[66] • Low (<0.2 nanomol/L) or
• Adults with type 1 diabetes absent C-peptide level.
typically present with • One or more auto-
hyperglycaemia and usually antibodies (antiglutamic
(but not always) one or more acid decarboxylase [GAD]
of: ketosis; rapid weight antibodies, islet cell
loss; age <50 years; BMI antibodies [ICA], insulin
<25 kg/m², personal and/or auto-antibodies, auto-
family history of autoimmune antibodies to the tyrosine
disease.[50] phosphates IA-2 and
IA-2beta) are present in 85%
of patients with type 1 at
the time of diagnosis, but
may disappear within a few
DIAGNOSIS
years.[52] Type 1 diabetes
is defined by the presence
of one or more of these
autoimmune markers, but
testing is usually not required
for diagnosis.
• Glucose screening
criteria cannot be used to
differentiate type 1 and
type 2 diabetes, as they are
identical.
Latent autoimmune • Typical age of onset of • Positive for at least 1 of

diabetes in adults (LADA) diabetes is over 30 years the 4 antibodies commonly
old. Patients are usually non- found in type 1 diabetic
obese and respond initially patients (ICAs and auto-
to lifestyle modifications and antibodies to GAD65, IA-2,
oral agents. Production of and insulin).[68]
insulin gradually decreases
(between 6 months and 5
years), such that treatment
with insulin is required.[67]
15

symptoms
• LADA is considered a subset
of type 1 diabetes; however,
patients with LADA are
frequently misclassified as
having type 2 diabetes.
Monogenic diabetes • The two main forms of • Genetic testing in

monogenic diabetes are patients with high index
maturity-onset diabetes of suspicion (genes
of the young (MODY) and encoding glucokinase and
neonatal diabetes mellitus transcription factors are
(NDM). identified).[72]
• MODY affects 1% to 2% of
people with diabetes.[69]
• MODY is caused by mutation
of a single gene (i.e.,
monogenic). As of 2011, at
least 11 forms of MODY are
known.[70]
• It has autosomal dominant
inheritance and should
be suspected in cases of
diabetes in non-obese,
young patients (adolescence
or young adult) with family
history of diabetes in
two or more successive
generations.[70]
• Patients are often
misclassified as type 1 or
type 2 diabetes. Insulin
treatment is often not
needed.[71]
DIAGNOSIS
Ketosis-prone diabetes • Presents with unprovoked • Absent islet cell auto-

ketosis or ketoacidosis antibodies.
but with a subsequent • C-peptide often low or
course that more closely undetectable during diabetic
mirrors type 2 than type 1 ketoacidosis; recovery may
diabetes.[44] [73] be used as reliable predictor
• Considered an 'idiopathic of insulin discontinuation.[74]
diabetes', as patients have
no evidence of autoimmunity.
Often misclassified as type
1 diabetes, as individuals
have episodic ketoacidosis
and exhibit varying degrees
of insulin deficiency between
episodes. However, a type
2 diabetes phenotype is
common in high-income
countries (obesity, insulin
resistance, metabolic
syndrome) although a similar
presentation has also been
seen in lean individuals in

symptoms
low-income countries.[44]
[74]
• Patients are usually from a
minority ethnic group, and
have a positive family history
of diabetes.[74]
• On discontinuation of insulin
therapy, the period of near-
normoglycaemic remission
may last for a few months
to several years. However,
almost half will be insulin
dependent 10 years after
diagnosis.[73]
Diabetes, gestational • Only occurs during • Gestational diabetes is

pregnancy. generally detected by
screening during pregnancy.
The UK National Institute for
Health and Care Excellence
recommends offering testing
for gestational diabetes
to any pregnant woman
with one or more of the
following risk factors:
BMI >30 kg/m²; previous
macrosomic baby weighing
≥4.5kg; previous gestational
diabetes; first-degree
relative with diabetes; ethnic
background associated
with high prevalence of
diabetes.[75]
DIAGNOSIS
• When overt hyperglycaemia
occurs during pregnancy, it
may be difficult to distinguish
between undetected pre-
existing type 2 diabetes and
gestational diabetes.
Criteria
World Health Organization criteria[44]
• Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL), or
• Plasma glucose ≥11.1 mmol/L (≥200 mg/dL) 2 hours after 75 g oral glucose, or
• Glycosylated haemoglobin (HbA1c) ≥48 mmol/mol (≥6.5%), or
• In a symptomatic patient, random plasma glucose of ≥11.1 mmol/L (≥200 mg/dL).
Bear in mind that a repeat confirmatory test is required in most cases, particularly in asymptomatic patients.
17
Screening
There is no routine population-level screening for type 2 diabetes in the UK.[76]
In the UK, the NHS Diabetes Prevention Programme (DPP) identifies people with modifiable risk factors
and non-diabetic hyperglycaemia, defined as HbA1c 42 to 47 mmol/mol (6.0% to 6.4%) or fasting plasma
glucose 5.5 to 6.9 mmol/L (99.0 to 124.2 mg/dL). Participants can self-refer or they might be identified by
another means (e.g., their medical records). The DPP offers tailored, personalised help, including education
on lifestyle choices, advice on how to reduce weight through healthier eating, and bespoke physical activity
programmes.[26]
The National Institute for Health and Care Excellence (NICE) in the UK recommends a two-stage strategy to
identify people at high risk of type 2 diabetes and those with undiagnosed type 2 diabetes: a risk assessment
and, if necessary, a confirmatory blood test.[11] NICE recommends that general practitioners (primary care
physicians) use a validated computer-based risk-assessment tool to identify people on their practice register
who may be at high risk of type 2 diabetes.[11] Risk assessment should be offered to:[11]
• All adults aged 40 and above (except pregnant women)

• People aged 25 to 39 of South Asian, Chinese, African-Caribbean, and black African ethnicity (except
pregnant women)
• Adults with any other condition that increases the risk of type 2 diabetes.
Those with a high risk score should be offered a fasting plasma glucose or HbA1c test; a blood test should
be considered regardless of risk score for those aged 25 and over of South Asian or Chinese descent whose
body mass index (BMI) is greater than 23 kg/m².[11]
Some other countries do have national screening programmes in place. For example, in the US:
• The US Preventive Services Task Force recommends screening for glucose status for adults ages 35
to 70 years who have BMI ≥25 kg/m²[77]
• The American Diabetes Association recommends routine screening of non-pregnant asymptomatic
adults of any age with BMI ≥25 kg/m² (≥23 kg/m² for people from Asia) plus one or more additional risk
factors for diabetes.[78]
DIAGNOSIS
Type 2 diabetes in adults Management
Approach
For updates on diagnosis and management of co-existing conditions during the pandemic, see our topic
'Management of co-existing conditions in the context of COVID-19'.
Diet and lifestyle are central to the management of type 2 diabetes. Offer structured education to the patient
(and/or their family members or carers) at and around the time of diagnosis, with annual reinforcement and
review.[55]
• Ongoing self-management education by a diabetes education nurse or dietitian promotes diabetes

self-care and supports beneficial lifestyle changes.[55] [79] [80] [81]
• This requires general nutrition and health lifestyle knowledge and an individualised nutrition and
exercise plan based on an initial assessment and treatment goals.
• Interventions that enhance self-management can significantly reduce diabetes distress.[82]
Care of adults with type 2 diabetes must include management of all major cardiovascular risk factors to
individualised targets. In addition to glucose control, this includes smoking cessation, blood pressure control,
lipid control, consideration of antiplatelet use for patients with high cardiovascular disease risk and steps
to reduce progression of diabetes-related kidney disease.[42] [55] [83] Use of antihyperglycaemic agents
(glucagon-like peptide-1 [GLP-1] receptor agonists and sodium-glucose co-transporter-2 [SGLT2] inhibitors)
that reduce cardiovascular or overall mortality or cardiovascular events may be especially beneficial in
those who have type 2 diabetes and established cardiovascular disease regardless of level of glucose
management.[42] [84]
• About 80% of adults with type 2 diabetes have concurrent dyslipidaemias or

hypertension.[5] Compared with people who are not obese, those with obesity are almost six times
more likely to develop diabetes.[85] Smoking prevalence among individuals with type 2 diabetes
is similar to that of the general population where current smokers are 25% versus 28% and never-
smokers 39% versus 42%, respectively.[86]
• On average, adults with type 2 diabetes are up to twice as likely to die of stroke or myocardial
infarction compared with those without diabetes, and they are more than 40 times more likely to die of
macrovascular than microvascular complications of diabetes.[87] [88] [89]
• However, data indicate that adults with type 2 diabetes who optimally manage glucose, blood
pressure, lipids, smoking, and weight have a risk of major cardiovascular events that is not significantly
above the risk of age and sex-matched peers without diabetes.[90] [91]
In addition, consider ACE inhibitors or angiotensin-II receptor antagonists for patients with chronic kidney
disease (CKD) or proteinuria.[55] Latest evidence among patients with type 2 diabetes and CKD also
indicates benefits of SGLT2 inhibitors in terms of slower progression of CKD, reduced cardiovascular events
and mortality, and lower all-cause mortality.[55] See Specific pharmacotherapy considerations for patients
with CKD.
Individualised care
Take an individualised approach to management that is tailored to the specific needs and circumstances
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of your patient. Take into account the patient’s:[55]
• Personal preferences
• Comorbidities
• Risks from polypharmacy
19
• Ability to benefit from long‑term interventions because of reduced life expectancy
• Disabilities (e.g., visual impairment).
This is particularly important in the context of multimorbidity.[55]
Use each review to reassess the patient’s needs and circumstances and consider whether to stop any
medicines that are not effective.[55]
Aim to make a routine assessment of frailty whenever you review an older person with diabetes.[58] [59]
[60] Use a validated tool (e.g., the electronic Frailty Index [eFI], the Rockwood frailty score, or Timed
Up and Go) to confirm clinical suspicion of frailty.[59] [60] Frail patients need a tailored approach to
management. Specifically bear in mind that:[58]
• Glycaemic targets recommended for good control in fit younger people are too tight for frail older
patients.[58] [59] To determine the most appropriate HbA1c target for your patient, check your local
protocols and consult a specialist if needed.
• The most appropriate drug regimens for a frail patient, including choice of drug and optimal dose,
will need careful consideration.[58] 'Start low and go slow' when dosing and titrating medications in
frail older adults.[58]
In practice, unless directed otherwise by a specific clinical need or dosing regimen, allow 3 to 6 months
to assess the impact of any intervention aimed at improving glycaemic control, whether pharmacological
or non-pharmacological. Bear in mind that this timeframe will vary on an individual patient basis; carefully
consider how much of a risk the patient’s HbA1c might pose and step up to more intense interventions
more quickly if needed.
Diet, physical activity, and sleep

Nutritional advice should be tailored to the needs of the individual patient, and be provided by a
healthcare professional with specific expertise and competencies in nutrition.[55]
Encourage the patient to:[55]
• Include high-fibre, low-glycaemic-index sources of carbohydrate in their diet, such as fruit,

vegetables, wholegrains, and pulses
• Eat low-fat dairy products and oily fish
• Limit their intake of foods containing saturated and trans fatty acids.
Give individualised recommendations for carbohydrate and alcohol intake, and meal patterns.
Reducing the risk of hypoglycaemia should be a particular aim for a person using insulin or an insulin
secretagogue.[55]
• Although limited substitution of sucrose-containing foods for other carbohydrates in the meal plan is
allowable, advise the patient to take care to avoid excess energy intake.[55]
• Discourage the patient from eating food marketed specifically for people with diabetes.[55]
• There is ongoing debate about the potential role of low-carbohydrate diets in people with type 2
diabetes.[42] Evidence suggests such diets can be safe and effective in the short term in managing
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weight, and improving glycaemic control and cardiovascular risk.[92] One meta-analysis found no
difference in glucose-lowering effects, weight, or low-density lipoprotein (LDL)-cholesterol levels
between low- and high-carbohydrate diets at 1 year or later.[93] Another meta-analysis concluded
there was moderate- to low-quality evidence that some patients can achieve remission of their type
2 diabetes by following a low-carb diet for 6 months.[94]
Integrate dietary advice with a personalised diabetes management plan that includes other aspects of
lifestyle modification, including increasing physical activity and losing weight.[95] [96] [97] [98] [99]
In terms of physical activity, encourage the patient to:
• Reduce sedentary behaviour and be more physically active[96]

• Incorporate activity into their daily life (e.g., brisk walking, gardening, cycling).[96] [98] In this way,
the patient can gradually increase the amount and intensity of activity they do.[96]
• Do at least 30 minutes of moderate (or greater intensity) physical activity on 5 or more days a
week.[98]
If the patient is overweight, set an initial body weight loss target of 5% to 10%.[55] Evidence suggests
this is the minimum weight loss in obese patients to improve glycaemic control, lipid levels, and blood
pressure.[42]
• Weight loss management programmes with a healthy eating and physical activity plan resulting in
an energy deficit have the potential for type 2 diabetes remission.[24] [100] [101]
• The Diabetes Remission Clinical Trial (DiRECT) of supported weight loss management for people
diagnosed with type 2 diabetes within the previous 6 years, and a body mass index (BMI) of 27kg/
m² to 45 kg/m², found that almost half of participants achieved remission to a non-diabetic state and
were off antidiabetic drugs at 12 months.[100] At 2 years, more than one third of trial participants
had sustained remission.[102]
An assessment of sleep duration and quality should be considered. Obesity, diabetes, hypertension, atrial
fibrillation, and male sex are risk factors for sleep apnoea, and inadequate sleep may affect glycaemic
control.[15]
Cardiovascular risk management

Blood pressure (BP)
Consult your local protocols. Guidelines differ regarding recommended blood pressure targets for those
with type 2 diabetes.
• The prevalence of hypertension is >60% in patients with type 2 diabetes.[42]

• Optimal BP control reduces the risk of both microvascular and macrovascular complications.[42]
The National Institute for Health and Care Excellence (NICE) in the UK recommends maintaining blood
pressure at:[57]
• Below 135/85 mmHg for adults aged under 80, based on ambulatory or home BP monitoring (or
<140/90 mmHg based on clinic BP)
• Below 145/85 mmHg for patients aged 80 and over, based on ambulatory or home BP monitoring
(or <150/90 mmHg based on clinic BP).
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The NICE guideline committee concluded that there was no evidence to suggest blood pressure targets
should be different in people with type 2 diabetes; these recommendations for blood pressure targets
apply to people with and without type 2 diabetes.[57] NICE also highlights the importance of measuring
standing as well as sitting blood pressure in people with type 2 diabetes, based on expert opinion that this
group of patients is at higher than usual risk of postural hypotension.[57]
21
The European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD)
guideline recommends:[42]
• A target systolic BP (SBP) in people with diabetes up to the age of 65 of 130 mmHg, and <130
mmHg if tolerated (but no lower than 120 mmHg)
• In older people (aged >65 years): SBP targeted to a range of 130 to 139 mmHg; a diastolic BP
(DBP) target of <80 mmHg (but not lower than 70 mmHg).
Regardless of the specific blood pressure goal, both lifestyle changes and antihypertensive medication
may be needed to achieve BP control. Reduced sodium intake (to <100 mmol/day) and high intake of fruit,
vegetables, and low-fat dairy products have all been shown to improve BP control.[42]
In the UK, NICE recommends a stepwise approach to pharmacological treatment of hypertension in

people without CKD, as follows.[57]
Step 1[57]
For initial treatment, give:
• An ACE inhibitor or an angiotensin-II receptor antagonist
• If an ACE inhibitor is not tolerated, use an angiotensin-II receptor antagonist instead

• Do not combine an ACE inhibitor with an angiotensin-II receptor antagonist
• An angiotensin-II receptor antagonist in preference to an ACE inhibitor if the patient is of black
African or African–Caribbean family origin.
Step 2[57]
If hypertension remains uncontrolled on first-line therapies:
• Discuss, and support, adherence with antihypertensive medication

• Step up to dual therapy: offer the choice of one of the following drugs in addition to step 1
treatment:
• A calcium-channel blocker, or
• A thiazide-like diuretic.
Step 3[57]
Before considering next step treatment, discuss adherence with the patient and review their medications
to ensure these are being taken at optimal tolerated doses.
If the patient’s blood pressure remains uncontrolled despite step 2 therapies, offer a triple therapy
combination of:
• An ACE inhibitor or an angiotensin-II receptor antagonist, and

• A calcium-channel blocker, and
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• A thiazide-like diuretic.
Step 4[57]
If blood pressure is not controlled despite optimal tolerated doses of the triple-therapy medications in step
3, regard the patient as having resistant hypertension. Refer these patients to a hypertension specialist.
If the patient has CKD and requires an antihypertensive agent, an angiotensin-II receptor antagonist
or ACE inhibitor may be the preferred option. Follow NICE guidelines on chronic kidney disease (see
Specific pharmacotherapy considerations for patients with CKD). Where possible, treat hypertension with
drugs taken only once daily.[57]
The ESC/EASD guideline takes a broadly similar approach to NICE but highlights additional key
messages:[42]
• There is strong evidence to support the use of an ACE inhibitor or angiotensin-II receptor
antagonist, particularly in patients who have microalbuminuria, proteinuria, or left ventricular
hypertrophy. These drugs have renoprotective properties that go beyond their antihypertensive
effects alone.
• Dual therapy is recommended as first-line treatment because most patients will not achieve BP
control on a single antihypertensive medication.
• Use of beta-blockers is not routinely recommended in patients with type 2 diabetes.
• In practice, beta-blockers may be considered if there are other compelling indications (e.g.,
coronary artery disease, atrial fibrillation, systolic heart failure).
There is an increasing drive to incorporate the use of home blood pressure monitoring into the diagnosis
and management of hypertension in adults, including those with diabetes.[57] [103]
Lipids
Consult your local protocols. Guidelines recommend differing approaches to lipid-modification therapy.
NICE and NHS England’s Accelerated Access Collaborative (NHSE AAC) recommend using:
• A validated risk assessment tool such as QRISK to assess cardiovascular disease (CVD) risk in
people with type 2 diabetes[104] [105] [QRISK calculator] (https://qrisk.org/three)
• High-intensity statin treatment for the primary prevention of CVD for people with type 2 diabetes
who have ≥10% 10-year risk (estimated using QRISK) of developing CVD[104] [105]
• Before starting lipid-modification therapy for the primary prevention of CVD, take at least
one lipid sample to measure a full lipid profile. This should include measurement of total
cholesterol, high-density lipoprotein (HDL)-cholesterol, non-HDL-cholesterol, and triglyceride
concentrations. A fasting sample is not needed[104] [105]
• The higher end of the dose range of a high-intensity statin is recommended for secondary
prevention if the patient has established CVD (provided they have normal renal
function).[104] [105]
Consistent data have demonstrated the efficacy of statins in preventing cardiovascular events and
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reducing cardiovascular mortality in patients with diabetes, with no evidence for sex differences; their use
is associated with a limited number of adverse events.[42]
In terms of monitoring, NICE and the NHSE AAC recommend the following.[104] [105]
23
• Measure total cholesterol, HDL-cholesterol, and non-HDL cholesterol in all people who have
been started on high-intensity statin treatment at 3 months of treatment and aim for a greater
than 40% reduction in non-HDL-cholesterol. Arrange for specialist assessment of people with a
total cholesterol concentration of more than 9.0 mmol/L (347.5 mg/dL) or a non-HDL-cholesterol
concentration of more than 7.5 mmol/L (289.6 mg/dL) even in the absence of a first-degree
family history of premature coronary heart disease. If a greater than 40% reduction in non-HDL-
cholesterol is not achieved:
• Discuss adherence and timing of dose

• Optimise adherence to diet and lifestyle measures
• Consider increasing the statin dose if the person is judged to be at higher risk because of
comorbidities, risk score, or based on clinical judgement.
• Review medication annually. Use these reviews to discuss medication adherence and lifestyle
modification and to address CVD risk factors. Consider an annual non-fasting blood test for non-
HDL-cholesterol to inform the discussion.
• Do not stop statins because of an increase in blood glucose level or HbA1c.
NICE recommends seeking specialist advice about suitable options for treating people with type 2
diabetes who are intolerant to three different statins.[104]
ESC/EASD guidelines categorise cardiovascular risk in patients with diabetes as:[42]
• Very high risk
• Patient with diabetes and any one or more of:
• Established cardiovascular disease

• Other target organ damage
• Three or more major risk factors (age, hypertension, dyslipidaemia, smoking, obesity)
• High risk
• Patients with diabetes duration ≥10 years without target organ damage plus any other
additional risk factor
• Moderate risk
• Patients with type 2 diabetes aged <50 years, with diabetes duration <10 years without other
risk factors.
Based on these categories, the ESC recommends in patients with type 2 diabetes who are:[42]
• At moderate cardiovascular risk: an LDL-cholesterol target of <2.6 mmol/L (<100 mg/dL)

• At high cardiovascular risk: an LDL-cholesterol target of <1.8 mmol/L (<70 mg/dL) and LDL-
cholesterol reduction of at least 50%; a secondary goal of a non-HDL-cholesterol target of <2.6
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mmol/L (<100 mg/dL)

• At very high cardiovascular risk: an LDL-cholesterol target of <1.4 mmol/L (<55 mg/dL) and LDL-
cholesterol reduction of at least 50%; a secondary goal of a non-HDL-cholesterol target of <2.2
mmol/L (<85 mg/dL).
The ESC recommends statins as first-line lipid-lowering treatment in patients with diabetes and high LDL-
cholesterol levels.[42] The cardiovascular risk profile (very high, high, moderate) of the individual patient
and the corresponding LDL-cholesterol (or non-HDL-cholesterol) target levels should be used to determine
statin administration.[42] If the recommended target LDL-cholesterol is not reached, consider intensifying
lipid-lowering therapy on an individual basis.[42]
For some patients with diabetes and established coronary heart disease who have persistently elevated
LDL despite maximally-tolerated statin therapy:
• Addition of ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (e.g.,

alirocumab, evolocumab) may confer clinical benefit[42] [106] [107] [108]
• Newer lipid-lowering therapies, such as bempedoic acid, may be considered for lipid-lowering, in
combination with either a statin or with a statin and other lipid-lowering therapies (e.g., ezetimibe).
Bempedoic acid can also be considered alone or in combination with other lipid-lowering therapies
in people who are statin-intolerant or for whom a statin is contraindicated.[109]
Smoking cessation
If the patient smokes, give advice on smoking cessation and information on accessing smoking cessation
services.[55] [110] [111]
Antiplatelet therapy
People with type 2 diabetes and CVD will need antiplatelet monotherapy for secondary prevention. This
will usually be in the form of low-dose aspirin or clopidogrel.[42] [112] Antiplatelet therapy has been found
to reduce the risk of stroke, mycardial infarction, or vascular death.[113]
The role of antiplatelets in primary prevention of CVD is unclear and guidelines differ in their
recommendations.[42] Consult your local protocols.
NICE recommends against routine antiplatelet therapy (aspirin or clopidogrel) for adults with type 2
diabetes without CVD.[55] This is because the increased risk of major bleeding is considered to outweigh
any potential benefits from primary prevention.[114] The ASCEND trial compared low-dose aspirin with
placebo among 15,480 adults with diabetes but no evident CVD. It found that the benefits of aspirin use
in preventing serious vascular events was largely counterbalanced by the increased risk of major bleeding
events over a mean follow-up of 7.4 years.[115]
However, the ESC/EASD guideline recommends to consider low-dose aspirin for primary prevention
of CVD in patients with diabetes who are at high/very high risk of CVD, provided there are no clear
contraindications:[42]
• Very high risk
• Patients with diabetes and:
• Established cardiovascular disease, or

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• Other target organ damage, or

• Three or more major risk factors (age, hypertension, dyslipidaemia, smoking, obesity).
• High risk
25
• Patients with diabetes duration ≥10 years without target organ damage plus any other
additional risk factor.
The ESC/EASD recommends to consider concomitant use of a proton-pump inhibitor in patients taking
low-dose aspirin to reduce the bleeding risk highlighted by the ASCEND trial (in which three-quarters of
patients were not taking a proton-pump inhibitor).[42]
The ESC/EASD does not recommend aspirin for primary prevention in patients at mild-moderate
risk of CVD (e.g., patients aged <50 years with type 2 diabetes duration <10 years without other risk
factors).[42]
Specific pharmacotherapy considerations for patients with CKD

If your patient with type 2 diabetes has chronic kidney disease (CKD) or develops it at any point post-
diagnosis, NICE recommends to:
• Give an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the highest licensed dose
that the person can tolerate) if albumin-to-creatinine ratio (ACR) is 3 mg/mmol or more[55] [63]
• Give an SGLT2 inhibitor (in addition to the angiotensin-II receptor antagonist or ACE inhibitor) if the
patient is already taking an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the
highest licensed dose that they can tolerate) and:[55]
• ACR is over 30 mg/mmol and

• The patient meets the criteria in the marketing authorisation (including relevant estimated
glomerular filtration rate [eGFR] thresholds)
• Consider an SGLT2 inhibitor (in addition to the angiotensin-II receptor antagonist or ACE inhibitor) if
the patient is already taking an angiotensin-II receptor antagonist or an ACE inhibitor (titrated to the
highest licensed dose that they can tolerate) and:[55]
• ACR is between 3 and 30 mg/mmol and

• The patient meets the criteria in the marketing authorisation (including relevant estimated
glomerular filtration rate [eGFR] thresholds).
If the patient has CKD and requires an antihypertensive agent, also follow the recommendations outlined
here (instead of the standard stepwise approach to blood pressure management for people without CKD).
Where possible, treat hypertension with drugs taken only once daily.[57]
These drugs should be added to optimised standard care (see Antihyperglycaemic pharmacotherapy
sections).
SGLT2 inhibitors are not suitable for everyone and should only be used within their marketing
authorisation; some SGLT2 inhibitors are not licensed for this indication in some regions, including the
UK.[55]
These recommendations from NICE are based on evidence from randomised controlled trials which
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showed that:
• SGLT2 inhibitors reduce the risk of CKD progression, mortality and cardiovascular events in adults
with type 2 diabetes and CKD.[55]
• Angiotensin-II receptor antagonists reduce the risk of end-stage renal disease and heart failure.[63]
• There is no clear difference between ACE inhibitors and angiotensin-II receptor antagonists on
a number of outcomes, including end-stage renal disease, all-cause mortality, cardiovascular
mortality, and hospitalisation.[63]
Antihyperglycaemic pharmacotherapy: overarching principles

HbA1c goals should be individualised at all stages of management; ensure the patient is involved in any
decisions about their individual glycaemic target.[116] [117] [118]
• Individualised HbA1c goals improve quality of life compared with uniform tight control.[117]
In the UK, NICE recommends:[118]
• If the patient manages their type 2 diabetes either with lifestyle and diet, or with lifestyle and diet
combined with a single drug that is not associated with hypoglycaemia, support them to aim for an
HbA1c level of 48 mmol/mol (6.5%)
• If the patient is on a drug associated with hypoglycaemia, support them to aim for an HbA1c level of
53 mmol/mol (7.0%).
Consider a slightly higher HbA1c level on a case-by-case basis for:[95]
• Patients who are older or frail

• Patients who are unlikely to achieve longer-term risk-reduction benefits (e.g., those with a reduced
life expectancy)
• Patients for whom tight blood glucose control poses a high risk of the consequences of
hypoglycaemia, including: people who are at risk of falling; people who have impaired awareness of
hypoglycaemia; those who drive or operate machinery as part of their job
• Patients for whom intensive management is not appropriate (e.g., people with significant
comorbidities).
Bear in mind that the most appropriate drug regimens for a frail patient, including choice of drug and
optimal dose, will need careful consideration and are likely to differ from those recommended for younger,
fit patients.[58]
If the patient drives, ensure they are aware of the relevant local advice on plasma glucose level. In the
UK, the Driver and Vehicle Licensing Agency advises to aim for a level of at least 5 mmol/L (90 mg/dL)
before driving.[119]
Regular self-monitoring of blood glucose (SMBG; finger stick blood glucose testing) may help with self-
management and medication adjustment, particularly in people taking insulin. SMBG can give insight into
the impact of lifestyle and medication management on blood glucose and symptoms, particularly when
combined with education and support; SMBG plans should be individualised.[120]
• NICE and the European Association for the Study of Diabetes/American Diabetes Association
(EASD/ADA) recommend SMBG as an option for people with type 2 diabetes who are using
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insulin.[118] [120]
• NICE also recommends routinely offering SMBG for adults with type 2 diabetes if:[118]
• There is evidence of hypoglycaemic episodes, or
27
• The patient is on oral medication that may increase their risk of hypoglycaemia while driving
or operating machinery, or
• The patient is pregnant, or is planning to become pregnant.
• NICE recommends considering short-term SMBG in adults with type 2 diabetes (and reviewing
treatment as necessary):[118]
• When starting treatment with oral or intravenous corticosteroids, or

• To confirm suspected hypoglycaemia.
Novel technologies, such as continuous or flash glucose monitoring, provide more information than
SMBG. However, continuous or flash glucose monitoring might not be readily available in all regions for
people with type 2 diabetes.
If the patient is unable to meet their individualised HbA1c goal with lifestyle interventions,
pharmacotherapy is recommended to reduce risk of both microvascular (nephropathy, retinopathy,
neuropathy) and macrovascular (myocardial infarction, stroke, peripheral vascular disease)
complications.[121] [122]
• Data suggest that preventing major cardiovascular events and renal complications of diabetes may
be affected not only by HbA1c levels but also by strategic selection of specific antihyperglycaemic
medications.
• Some specific antihyperglycaemic medications significantly reduce all-cause or cardiovascular
mortality, or major cardiovascular events or renal complications or hospitalisations for heart failure
in some patient subgroups, and for such patients, these agents may be preferred.[84] Among the
antihyperglycaemic medications that reduce cardiovascular mortality in some patient subgroups are
metformin, empagliflozin, and liraglutide.[84] [123]
In older studies such as ACCORD, ADVANCE, and the Veterans Affairs Diabetes Trial, use of multiple
drugs to achieve near-normal HbA1c was either not beneficial or increased mortality in type 2 diabetes
patients with CVD or high CVD risk.[124] [125] [126] [127] [128] However, SGLT2 inhibitors were not
available and GLP-1 receptor agonists were infrequently used in those studies.
Choice of agents should be individualised, taking into account patient values and preferences, the
likelihood that an agent reduces all-cause or cardiovascular mortality, renal effects, adverse effects, and
other factors.[55] [120] [129]
If an adult with type 2 diabetes is symptomatically hyperglycaemic at any phase of treatment, consider
rescue therapy with insulin or a sulfonylurea, and review treatment when blood glucose control has been
achieved.[55]
In the UK, NICE recommends a glucocentric step-wise approach to the management of adults with type
2 diabetes, with SGLT2 inhibitors and GLP-1 receptor agonists generally only recommended as second-
line options for people with elevated glucose levels after metformin treatment.[55] The recommendations
in this topic are based primarily on the NICE approach.
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However, since the publication of the NICE guideline, some treatment strategies have shifted to a
focus on the absolute reduction of cardiovascular and kidney disease outcomes instead of being led
by glycaemic control. This is based on evidence from high-quality randomised trials demonstrating
atherosclerotic CVD and chronic kidney disease (CKD) benefits independent of medications’ glucose-
lowering potential.[129] In particular, SGLT2 inhibitors appear to have benefits in patients with type 2
diabetes who have more than three risk factors for CVD, and both SGLT2 inhibitors and GLP-1 receptor
agonists appear beneficial in those with established CVD and/or renal disease.[125] [128] [130] [BMJ:
SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes] (https://www.bmj.com/
content/373/bmj.n1091) NICE updated its guideline in November 2021 to recognise a separate role for
SGLT2 inhibitors - regardless of glycaemic control - for patients with CKD whose albumin-to-creatinine
ratio is above a specified level despite treatment with an ACE inhibitor or angiotensin-II receptor
antagonist. See Specific pharmacotherapy considerations for patients with CKD.
Antihyperglycaemic pharmacotherapy: initial treatment

If HbA1c rises to 48 mmol/L (6.5%; or the patient’s individualised goal) on lifestyle interventions,
NICE recommends to give immediate-release metformin as first-line therapy in the absence of
contraindications.[55]
• Always use an appropriate HbA1c target for the individual patient.

• Metformin is the recommended first choice because of its safety profile, its likely cardiovascular
benefit, and the long-term experience in its use.[121] [123]
• Metformin may be safely used (with a possible dose reduction) in patients with reduced estimated
glomerular filtration rates (eGFRs), but it is contraindicated if eGFR <30 mL/minute/1.73 m².[15]
[120]
• Review the dose of metformin if the eGFR is below 45 mL/minute/1.73 m².[55]
• Stop metformin if the eGFR is below 30 mL/minute/1.73 m².

• Prescribe metformin with caution for those at risk of a sudden deterioration in kidney function
and those at risk of eGFR falling below 45 mL/minute/1.73 m².
If metformin is contraindicated or not tolerated, consider initial drug treatment with:[55]
• A dipeptidyl peptidase-4 (DPP-4) inhibitor (e.g., alogliptin, linagliptin, saxagliptin, sitagliptin), or

• Pioglitazone (a thiazolidinedione), or
• A sulfonylurea (e.g., gliclazide, glimepiride).
Pioglitazone is not a suitable option if the patient has any of:[55]
• Heart failure or history of heart failure

• Hepatic impairment
• Diabetic ketoacidosis
• Current, or a history of, bladder cancer
• Uninvestigated macroscopic haematuria.
NICE recommends monotherapy with an SGLT2 inhibitor (e.g., canagliflozin, dapagliflozin, empagliflozin,
ertugliflozin) as an option for patients in whom metformin is contraindicated or not tolerated, when diet
and exercise alone do not provide adequate glycaemic control, and only if:[55] [131] [132]
• A DPP-4 inhibitor would otherwise be prescribed, and

• A sulfonylurea or pioglitazone is not appropriate.
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In practice, monotherapy with an SGLT2 inhibitor or a GLP-1 receptor agonist (e.g., dulaglutide,
exenatide, liraglutide, lixisenatide, semaglutide) is increasingly used as a first-line alternative to
metformin. This is because of evidence demonstrating the CVD and renal benefits of these drug
classes, independent of their glucose-lowering effects.[130] A 2019 update to a joint consensus report
29
from the American Diabetes Association and the European Association for the Study of Diabetes
recommends:[129]
• If a patient with type 2 diabetes has established CVD, there is a compelling indication for treatment
with a GLP-1 receptor agonist or SGLT2 inhibitor
• If a patient with type 2 diabetes is at high risk of CVD, consider treatment with a GLP-1 receptor
agonist or SGLT2 inhibitor independently of their baseline HbA1c or individualised HbA1c target
with the aim of reducing major cardiovascular events or death and slowing progression of kidney
impairment.
• A November 2021 update to the NICE guideline also highlights a role for SGLT2 inhibitors in
slowing the progression of CKD in specific groups of patients with diabetes.[55]
In practice, if the patient has CKD with eGFR >45 mL/minute/1.73 m², it may be appropriate for them to
take an SGLT2 inhibitor for both antihyperglycaemic and renal benefit (see Specific pharmacotherapy
considerations for patients with CKD for advice on when to use an SGLT2 inhibitor in people with CKD).
However, if the patient has CKD with eGFR <45 mL/minute/1.73 m², the glucose-lowering effects of
SGLT2 inhibitors will be negligible and therefore they will need an alternative antihyperglycaemic agent for
initial glucose-lowering therapy.[133]
Antihyperglycaemic pharmacotherapy: first intensification

If HbA1c rises to the patient’s agreed threshold for intensification (typically 58 mmol/mol [7.5%] but
may be individualised according to the patient’s circumstances) despite initial drug treatment, NICE
recommends to support the patient to aim for an HbA1c level of 53 mmol/mol (7.0%) and consider dual
therapy with:[55]
• Metformin and a DPP-4 inhibitor, or

• Metformin and pioglitazone, or
• Metformin and a sulfonylurea.
Combination treatment with metformin and an SGLT2 inhibitor may be appropriate in some patients with
type 2 diabetes (e.g., a sulfonylurea is contraindicated or not tolerated, the person is at significant risk
of hypoglycaemia or its consequences). In these situations, NICE recommends to consider the following
options:[55] [132] [134] [135] [136]
• Metformin and canagliflozin, or

• Metformin and dapagliflozin, or
• Metformin and empagliflozin, or
• Metformin and ertugliflozin.
If your patient does not have established CVD, choose an agent to combine with metformin according to
individual patient needs:[137]
• To avoid hypoglycaemia: a DPP-4 inhibitor or pioglitazone or an SGLT2 inhibitor

• For rapid glycaemic response, or if the patient is on corticosteroids: a sulfonylurea or insulin
MANAGEMENT
(ongoing or rescue therapy)

• For weight loss: an SGLT2 inhibitor
• In frail/older patients: a DPP-4 inhibitor. Avoid drugs causing hypoglycaemia and SGLT2 inhibitors
• If all factors are equal: pioglitazone or a sulfonylurea.
Bear in mind that SGLT inhibitors have minimal glycaemic benefit if eGFR <45 mL/minute/1.73 m² (as
might be the case if the patient has CKD).[133]
If the patient has established atherosclerotic CVD, the ESC/EASD recommends dual therapy of metformin
with either:[42]
• An SGLT2 inhibitor with CVD benefits (strongest evidence is for canagliflozin, dapagliflozin, and
empagliflozin), or
• A GLP-1 receptor agonist with CVD benefits (strongest evidence for cardiovascular mortality benefit
is for liraglutide; semglutide and dulaglutide have also been shown to reduce cardiovascular events
in patients with diabetes and CVD, and in those who are at very high/high cardiovascular risk).
NICE is in the process of updating its recommendations on choice of first intensification medication after
its evidence review highlighted the importance of comorbidities including CVD, heart failure, and CKD in
informing the most beneficial choice of medication for the patient.[138]
If metformin is contraindicated or not tolerated and initial drug treatment has not continued to control
HbA1c to below the patient’s individually agreed threshold for intensification, NICE recommends to
consider dual therapy with:[55]
• A DPP-4 inhibitor and pioglitazone, or

• A DPP-4 inhibitor and a sulfonylurea, or
• Pioglitazone and a sulfonylurea.
Bear in mind that drugs in dual therapy should be introduced in a stepwise manner, checking for
tolerability and effectiveness of each drug.[55]
Antihyperglycaemic pharmacotherapy: second intensification

If, despite dual therapy with metformin and another oral drug (see 'Antihyperglycaemic pharmacotherapy:
first intensification' above), HbA1c rises to the patient’s agreed threshold for intensification (typically 58
mmol/mol [7.5%] but may be individualised according to the patient’s circumstances), NICE recommends
to support the patient to aim for an HbA1c level of 53 mmol/mol (7.0%) and consider either:[55]
• Triple therapy with:
• Metformin, a DPP-4 inhibitor, and a sulfonylurea, or

• Metformin, pioglitazone, and a sulfonylurea, or
• Metformin, pioglitazone or a sulfonylurea, and an SGLT2 inhibitor
• Starting insulin-based treatment.
If this approach is not effective, not tolerated, or contraindicated, consider combination therapy with
metformin, a sulfonylurea, and a GLP-1 receptor agonist for adults with type 2 diabetes who:[55]
• Have a BMI of 35 kg/m² or higher (adjust accordingly for people from black, Asian, and other
minority ethnic groups) and specific psychological or other medical problems associated with
MANAGEMENT
obesity, or
• Have a BMI lower than 35 kg/m² and for whom:
• Insulin therapy would have significant occupational implications, or
31
• Weight loss would benefit other significant obesity-related comorbidities.
Only continue GLP-1 receptor agonist therapy if the patient has had a beneficial metabolic response (a
reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight
in 6 months).[55]
Bear in mind that SGLT inhibitors have minimal glycaemic benefit if eGFR <45 mL/minute/1.73 m² (as
might be the case in people with CKD).[133]
If metformin is contraindicated or not tolerated, and if dual therapy with two oral drugs (a DPP-4 inhibitor
and pioglitazone, or a DPP-4 inhibitor and a sulfonylurea, or pioglitazone and a sulfonylurea) has not
continued to control HbA1c to below the patient’s individually agreed threshold for intensification, NICE
recommends to consider insulin-based treatment.[55] See 'Antihyperglycaemic pharmacotherapy: insulin-
based treatments' below.
Give careful consideration to the drug combinations, ensuring that they are safe and appropriate for your
patient. If possible, avoid combining insulin with pioglitazone. The UK Medicines and Healthcare products
Regulatory Agency (MHRA) warns that patients should be observed for signs and symptoms of heart
failure, weight gain, and oedema if pioglitazone is used in combination with insulin. This is owing to the
increased incidence of cardiac failure when pioglitazone is used in combination with insulin, especially in
patients with predisposing factors.[139]
Only offer a GLP-1 receptor agonist in combination with insulin with specialist care advice and ongoing
support from a consultant-led multidisciplinary team.[55] The MHRA warns of cases of diabetic
ketoacidosis in patients with type 2 diabetes on a combination of a GLP-1 receptor agonist and insulin
who had doses of concomitant insulin rapidly reduced or discontinued.[140]
Clinical properties of specific oral antihyperglycaemic agents

Select agents on a case-by-case basis, following careful discussion with the patient of the pros and cons
of each option. Agents that reduce all-cause or cardiovascular mortality may be preferred.[42] [120] [129]
• Metformin can promote weight loss and may reduce cardiovascular events and mortality.[121] [123]
• SGLT2 inhibitors inhibit renal glucose reabsorption. The resulting increase in glycosuria
improves glycaemic control, promotes weight loss, and has a diuretic effect that reduces blood
pressure.[141] Empagliflozin and canagliflozin have been shown to reduce cardiovascular risk in
people with CVD and type 2 diabetes, and may have renal benefits.[84] [142] [143] [144] [145] The
CREDENCE trial demonstrated a clear benefit of canagliflozin on multiple renal end points,
including progression to end-stage kidney disease, and on cardiovascular mortality, major adverse
cardiovascular events (MACE), and hospitalisation for heart failure (HF).[146] Empagliflozin has
been shown to significantly reduce cardiovascular or all-cause mortality in those with diabetes
and established cardiovascular disease; canagliflozin has been shown to reduce MACE in this
group.[147] [148] [149] In the DECLARE-TIMI 58 trial, treatment with dapagliflozin in patients with
type 2 diabetes who had, or were at risk for, atherosclerotic cardiovascular disease did not result
in a lower rate of major adverse cardiovascular events, but did report a lower rate of hospitalisation
MANAGEMENT
for heart failure.[150] Further analysis of two of these large SGLT2 inhibitor cardiovascular
outcomes trials (DECLARE-TIMI 58 and CANVAS) suggests that the benefits of SGLT2 inhibitors
for hospitalisation for HF, MACE, and cardiovascular death are greatest for people with pre-existing
heart failure with reduced ejection fraction (HFrEF) compared with those without HFrEF.[142] [148]
[149] [150] [151] [152] In these trials, hospitalisation for HF was a secondary outcome, relatively
low numbers of patients had HF at baseline, and data on ejection fraction were only available
for a proportion of patients.[129] The DAPA-HF trial in patients with heart failure with reduced
ejection fraction found that dapagliflozin reduced the risk of worsening heart failure or death from a
cardiovascular cause, both among the group who had diabetes and among those who did not.[153]
[154] Trials on the CVD benefits of ertugliflozin are ongoing; to date, the data show non-inferiority
to standard care but no superiority in cardiovascular outcomes, unlike the other investigated SGLT2
inhibitors.[155] [156] [157]
• A 2019 update to a consensus report from the American Diabetes Association (ADA) and
the European Association for the Study of Diabetes (EASD) concluded that evidence now
supports the benefits of specific SGLT2 inhibitors in reducing MACE, hospitalisation for HF,
cardiovascular death, and CKD in high-risk patients with type 2 diabetes independently
of baseline HbA1c or individualised HbA1c target.[120] [129] The ADA/EASD specifically
recommends:[129]
• SGLT2 inhibitors in patients with type 2 diabetes and heart failure (particularly those
with heart failure with reduced ejection fraction) to reduce hospitalisation for HF,
MACE, and CVD death
• SGLT2 inhibitors in patients with type 2 diabetes with CKD (eGFR 30 to ≤60 mL/
minute/1.73 m² or urinary albumin to creatinine ratio >30 mg/g, particularly >300 mg/g)
to prevent the progression of CKD, hospitalisation for HF, MACE, and cardiovascular
death.
• GLP-1 receptor agonists are suitable for obese patients without gastroparesis who desire
weight loss, are willing to take injections, and can tolerate the common adverse effect of initial
nausea.[158] In one review, GLP-1 receptor agonist use led to loss of 1.4 kg versus placebo,
and loss of 4.8 kg versus insulin.[159] To date, the level of evidence to support the use of GLP-1
receptor agonists for primary prevention is strongest for dulaglutide but lacking for other GLP-1
receptor agonists.[129] Dulaglutide and semaglutide have both been shown to reduce major
cardiovascular events, but not all-cause or cardiovascular mortality.[160] [161] [162] Liraglutide
significantly reduced cardiovascular mortality and all-cause mortality in those with diabetes and
cardiovascular disease or high CVD risk in one randomised trial.[163] Exenatide and lixisenatide
have both been shown not to reduce major cardiovascular events.[164] The 2019 update to
a consensus report from the ADA/EASD concluded that evidence now supports the benefits
of specific GLP-1 receptor agonists in reducing MACE, hospitalisation for HF, cardiovascular
death, and CKD in high-risk patients with type 2 diabetes independently of baseline HbA1c or
individualised HbA1c target.[120] [129]
• The ESC/EASD recommends the use of GLP-1 receptor agonists to reduce cardiovascular
events in type 2 diabetes patients with established atherosclerotic CVD where MACE is the
gravest threat.[42] [120] [129]
• The ADA/EASD recommends considering GLP-1 receptor agonists in patients with type 2
diabetes without established CVD but with the presence of specific indicators of high risk:
MANAGEMENT
patients aged 55 years or older with coronary, carotid, or lower-extremity artery stenosis
>50%; left ventricular hypertrophy; an eGFR <60 mL/minute/1.73 m²; or albuminuria.[129]
• DPP-4 inhibitors are well tolerated and weight-neutral, but confer no mortality benefit. Sulfonylureas
are the subject of long clinical experience and may reduce microvascular complications, but confer
no mortality benefit and may cause weight gain and hypoglycaemia.[120] The CAROLINA trial
33
randomised adults at high cardiovascular risk to receive either the DPP-4 inhibitor linagliptin or the
sulfonylurea glimepiride to evaluate a primary MACE end point. The trial demonstrated no between-
group difference in the primary end point. At trial end, for linagliptin as compared with glimepiride,
there was a 1.5 kg weight loss benefit, no difference in HbA1c or introduction of glucose-lowering
medications post-baseline, and substantial benefits in terms of reductions in hypoglycaemia
(serious hypoglycaemic events were rare with glimepiride).[165]
• Pioglitazone lowers blood sugar effectively but more than doubles the risk of congestive heart
failure, often causing weight gain and oedema.[120] Pioglitazone may cause anaemia and increase
fracture rates in both women and men. Use of pioglitazone is associated with a small increased
risk of bladder cancer.[166] Another thiazolidinedione, rosiglitazone, has been removed from
the European market due to persistent safety concerns, but it may still be available in other
countries.[167]
• Adverse effects for different agents have included a higher rate of genital infections, acute kidney
injury, fracture, and/or amputation.[147] [168] [169]
• Notably, there is a risk for euglycaemic diabetic ketoacidosis with all SGLT2 inhibitors.[49]
[170] [171]
• The MHRA and the European Medicines Agency warn of an increased risk of lower-limb
amputation (mainly toes) in patients with type 2 diabetes taking canagliflozin.[172] [173] This
was based on findings from the CANVAS trials.[142] [148] [149] However, this was not
seen in the subsequent CREDENCE trial.[146] The MHRA emphasises the importance of
preventive foot care for all patients with diabetes.[174] The ADA/EASD recommends that
patients with foot ulcers or at high risk for amputation should only be treated with SGLT2
inhibitors after careful shared decision-making around risks and benefits with comprehensive
education on foot care and amputation prevention.[129] Evidence does not show an
increased risk for dapagliflozin and empagliflozin, but the risk may be a class effect.
• The MHRA and the US Food and Drug Administration warn of cases of necrotising fasciitis of
the perineum (also known as Fournier's gangrene) observed in post-marketing surveillance
of SGLT2 inhibitors.[175] [176] Thus, SGLT2 inhibitors should be avoided in patients with
conditions that increase the risk for limb amputations, and in patients prone to urinary tract or
genital infections.
• The MHRA warns of cases of diabetic ketoacidosis in patients with type 2 diabetes on a
combination of a GLP-1 receptor agonist and insulin who had doses of concomitant insulin
rapidly reduced or discontinued.[140]
Antihyperglycaemic pharmacotherapy: insulin-based treatments

When starting insulin therapy, the patient should continue metformin as long as there are no
contraindications or intolerances. Review the continued need for other blood glucose-lowering
therapies.[55]
NICE recommends:[55]
MANAGEMENT
• Choose the most appropriate insulin type and individualised regimen

• Give basal isophane (NPH) insulin injected once or twice daily according to need
• Consider starting both NPH and short-acting insulin (particularly if the person's HbA1c is 75 mmol/
mol [9.0%] or higher), administered either:
• Separately, or
• As a pre-mixed (biphasic) human insulin preparation
• Consider using insulin detemir or insulin glargine as an alternative to NPH insulin if:
• The patient needs assistance from a carer or healthcare professional to inject insulin, and
use of insulin detemir or insulin glargine would reduce the frequency of injections from twice
to once daily, or
• The patient’s lifestyle is restricted by recurrent symptomatic hypoglycaemic episodes, or
• The patient would otherwise need twice-daily NPH insulin injections in combination with oral
glucose-lowering drugs
• Consider pre-mixed (biphasic) preparations that include short-acting insulin analogues, rather than
pre-mixed (biphasic) preparations that include short-acting human insulin preparations, if:[55]
• The patient prefers injecting insulin immediately before a meal, or

• Hypoglycaemia is a problem, or
• Blood glucose levels rise markedly after meals.
Consider switching to insulin detemir or insulin glargine from NPH insulin if the patient:[55]
• Does not reach their target HbA1c because of significant hypoglycaemia, or

• Experiences significant hypoglycaemia on NPH insulin irrespective of the level of HbA1c reached,
or
• Cannot use the device needed to inject NPH insulin but could administer their own insulin safely
and accurately if switched to one of the long-acting insulin analogues, or
• Needs help from a carer or healthcare professional to administer insulin injections and for whom
switching to one of the long-acting insulin analogues would reduce the number of daily injections.
If the patient is on a basal insulin regimen (NPH insulin, insulin detemir, or insulin glargine), monitor for
the need for short-acting insulin before meals (or a pre-mixed [biphasic] insulin preparation).[55]
If the patient is on pre-mixed (biphasic) insulin, monitor for the need for a further injection of short-acting
insulin before meals or for a change to a basal bolus regimen with NPH insulin or insulin detemir or insulin
glargine, if blood glucose control remains inadequate.[55]
Most people with type 2 diabetes will use insulin delivery devices (insulin pens).
• These can be adjusted to administer set doses of insulin, are widely available, and offer
convenience and accuracy in insulin dosing.
• Less frequently, insulin pumps and patch pump systems are used on a case-by-case basis in
people who need multiple daily dose insulin.
• Insulin pumps are typically reserved for people with type 1 diabetes. If an insulin pump is
appropriate for the patient, its use will require significant patient engagement to achieve clinical
benefits beyond multiple daily dose injection-based therapy.
Exogenous insulin is a very effective way to lower serum glucose and lower HbA1c, but its use must be
MANAGEMENT
guided in most patients by regular self-monitored blood glucose testing (finger stick blood glucose testing)
or continuous glucose monitoring.
35
• Hypoglycaemia (glucose ≤3.9 mmol/L [≤70 mg/dL]) is the most serious potential complication of
insulin therapy. People who drive need to be particularly careful to avoid hypoglycaemia and should
be warned of the dangers. See the 'Complications' section of this topic.
• Another significant side effect is weight gain.
• Less common side effects may include hunger, nausea, diaphoresis, injection site irritation, or
anaphylaxis.
Correction doses of insulin

When basal-bolus insulin is used by motivated and knowledgeable patients, the dose of rapid-acting
insulin that is administered before each meal can be based on anticipated carbohydrate content of the
upcoming meal and sometimes adjusted for anticipated physical activity.
A correction (or adjustment) dose may be added to the bolus insulin based on the pre-meal blood glucose
level. In practice, a conservative approach to calculating a correction dose is to assume 1 unit of insulin
will lower the patient’s blood glucose by 2 to 4 mmol/L (36-72 mg/dL). Correction dosing can also be
calculated using the patient's total daily dose of insulin if food intake is stable. The correction dose can be
added to the patient's mealtime insulin requirement (whether based on general meal size or carbohydrate
counting) and given as the total bolus dose.
Alternatives to a basal-bolus insulin regimen

While NICE recommends consideration of a basal-bolus insulin regimen for patients who are unable to
maintain glycaemic targets on basal insulin alone, the ADA/EASD also recommends an alternative option
of adding a GLP-1 receptor agonist or an SGLT2 inhibitor to basal insulin to intensify treatment.[120]
[129] Such regimens should only be initiated by a diabetes specialist.
• This is particularly recommended for patients who are obese and will require high doses of insulin
because of insulin resistance, making the side-effect of weight gain from insulin use especially
problematic.
• Evidence shows that an SGLT2 inhibitor can be added to basal insulin to lower blood glucose
without any weight gain or hypoglycaemia.[177] [178] [179]
• Trial data also supports the combination of basal insulin and a GLP-1 receptor agonist to lower
HbA1c and limit weight gain and hypoglycaemia when compared with an intensified insulin
regimen.[180] [181]
Sick-day rules
Ensure the patient is aware that any intercurrent illness can cause glucose levels to rise.[182] Give the
patient clear and individualised oral and written advice (‘sick-day rules’) about how to adapt management
during intercurrent illness. Some drugs need to be suspended during intercurrent illness; it is important to
ensure the patient is aware that they will need to restart any suspended medication once they are feeling
better and able to eat and drink. [DiabetesontheNet: sick day rules] (https://diabetesonthenet.com/wp-
content/uploads/pdf/dotn024ae8fb1b78500b7bc752b98e9b6d92.pdf)
MANAGEMENT
The SADMANS mnemonic can be helpful as a reminder of drugs to temporarily pause during sick days,
where the illness leads to dehydration:[183]
• S - sulfonylureas
• A - ACE inhibitors
• D - diuretics, direct renin inhibitors
• M - metformin
• A - angiotensin-II receptor antagonists
• N - non-steroidal anti-inflammatory drugs
• S - SGLT2 inhibitors
If an adult with type 2 diabetes is unwell, consider the need to arrange hospital admission or seek
specialist advice. Use your clinical judgement, and take into account the patient’s age, frailty,
comorbidities, and risk of complications, and the presence of hyperglycaemia, hypoglycaemia, and/or
ketosis.
• Bear in mind that there is a considerable risk of hypoglycaemia in some patients. This is a
particular concern in patients who are older and/or frail, those with reduced appetite (and
subsequent reduced oral intake) owing to acute illness, and those taking medications that put them
at specific risk of hypoglycaemia (e.g., sulfonylureas and insulin). These patients will need close
blood glucose monitoring and may require medication adjustments.
Bariatric surgery for treatment of diabetes in patients with

obesity
Guidelines from NICE recommend:[98]
• Offer an expedited assessment for bariatric surgery to anyone with a BMI of 35 or over who has
recent-onset type 2 diabetes (diagnosis within last 10 years) as long as they are also receiving or
will receive assessment by a clinician-led community-based multidisciplinary team (a ‘tier 3’ service
in the UK)
• Consider an assessment for bariatric surgery for anyone with a BMI of 30 to 34.9 kg/m² who has
recent-onset type 2 diabetes as long as they are also receiving or will receive assessment in a ‘tier
3’ service (or equivalent)
• Consider an assessment for bariatric surgery for anyone of Asian family origin who has recent-
onset type 2 diabetes at a lower BMI than other populations as long as they are also receiving or
will receive assessment in a ‘tier 3’ service (or equivalent)
• People of Asian family origin have comorbidity risk factors that are of concern at lower BMIs.
The 2018 ADA/EASD consensus guideline recommends bariatric surgery as an option for patients with
type 2 diabetes who have:[120]
• A BMI ≥40.0 kg/m² if of non-Asian ancestry

• A BMI ≥37.5 kg/m² if of Asian ancestry
• A BMI of 35.0 to 39.9 kg/m² (32.5 to 37.4 kg/m² if of Asian ancestry) and who cannot achieve
durable weight loss with non-surgical methods.
Randomised clinical trials have shown a benefit from bariatric surgery (also referred to as metabolic
surgery) compared with medical therapy alone with regard to diabetes remission, glycaemic control, need
MANAGEMENT
for glucose-lowering medications, quality of life, and reduction in cardiovascular risk factor markers over
the short term (e.g., 1-3 years) in people with type 2 diabetes, as well as for possible prevention of type 2
diabetes.[184] [185] [186] [187] [188] [189]
37
• Cohort studies suggest that both Roux en Y bypass and sleeve gastrectomy procedures lead to
diabetes remission that lasts a mean of about 5 years in more than half of patients, and significantly
reduce mortality, stroke, myocardial infarction, and microvascular complications in those with type 2
diabetes.[190] [191] [192]
• Compared with sleeve gastrectomy, Roux en Y leads to somewhat greater weight loss and other
benefits, but is a more technically challenging operation with higher re-operation and readmission
rates.
• The benefits and risks of bariatric surgery also vary substantially across type 2 diabetes patient
subgroups. In observational studies, average benefits appear to be highest in people with more
recent onset of type 2 diabetes, and those not on insulin therapy.[172] [193] Benefits have been
documented in younger people (age 40-50 years) as well as those over 65 years of age.[172] [193]
Planning pregnancy
Women with type 2 diabetes should use an effective method of contraception until they plan
pregnancy.[16] Women should be evaluated before pregnancy for retinopathy, nephropathy, neuropathy,
and possible cardiovascular disease, which may worsen during or complicate pregnancy.[16]
Explain to women with diabetes who are planning pregnancy that:[16]
• If they have good blood glucose control before conception and throughout their pregnancy, this will
reduce the risk of miscarriage, congenital malformation, stillbirth, and neonatal death
• The risks can be reduced but not eliminated.
Agree individualised targets for self-monitoring of blood glucose with women who have diabetes and are
planning a pregnancy, taking into account the risk of hypoglycaemia.[16]
NICE recommends that HbA1c should be <48 mmol/mol (6.5%) before conception if this can be achieved
without problematic hypoglycaemia.[16] Any reduction towards this target is likely to reduce the risk of
congenital malformations. NICE recommends up to monthly measurement of HbA1c levels for women
with diabetes who are planning a pregnancy.[16]
• Strongly advise women with diabetes whose HbA1c level is above 86 mmol/mol (10%) not to get
pregnant until their HbA1c level is lower, because of the associated risks.[16]
Review the patient’s medication. Stop any drugs contraindicated in pregnancy if your patient is planning
pregnancy or as soon as pregnancy is confirmed; use alternative agents that are suitable for pregnant
women.
• Women with diabetes may be advised to use metformin (with or without insulin) in the
preconception period (and during pregnancy), when the likely benefits from improved blood glucose
control outweigh the potential for harm. Stop all other oral blood glucose-lowering agents before
pregnancy.[16]
• Stop ACE inhibitors and angiotensin-II receptor antagonists before conception, or as soon as
pregnancy is confirmed.[16]
MANAGEMENT
• Stop SGLT2 inhibitors if the patient is planning pregnancy, or as soon as pregnancy is

confirmed.[133]
• Stop statins before pregnancy, or as soon as pregnancy is confirmed.[16]
Advise women who are planning a pregnancy to take folic acid, which should be continued until 12 weeks
of gestation.[16]
• Women with diabetes have an increased risk of having infants with neural tube defects, compared
with the general population.[194]
During pregnancy
During pregnancy, women should be cared for by a multidisciplinary team, including a dietitian, a nurse
educator, an endocrinologist, and an obstetrician.
Offer pregnant women with pre-existing diabetes retinal assessment by digital imaging with mydriasis
using tropicamide following their first antenatal clinic appointment (unless they have had a retinal
assessment in the last 3 months), and again at 28 weeks. If any diabetic retinopathy is present at
booking, perform an additional retinal assessment at 16 to 20 weeks.[16]
NICE guidelines recommend the following blood glucose targets in pregnant women with pre-existing type
2 diabetes (as long as these are achievable without causing problematic hypoglycaemia):[16] [Evidence
C]
• Fasting: <5.3 mmol/L (<95.4 mg/dL), and

• 1 hour after meals: <7.8 mmol/L (<140.4 mg/dL), or
• 2 hours after meals: <6.4 mmol/L (<115.2 mg/dL).
Advise pregnant women with diabetes who are on insulin to maintain their capillary plasma glucose level
above 4 mmol/L (72 mg/dL).[16]
Measure HbA1c levels in all pregnant women with pre-existing diabetes at the booking appointment
to determine the level of risk for the pregnancy. Consider measuring HbA1c levels in the second and
third trimesters of pregnancy for women with pre-existing diabetes to assess the level of risk for the
pregnancy.[16]
• Good glucose control with HbA1c as close to normal as is safely possible (ideally HbA1c <48
mmol/mol [<6.5%]) before conception and during pregnancy optimises maternal and fetal health
outcomes.[16]
Review the patient’s medication. Stop any agents contraindicated in pregnancy as soon as pregnancy is
confirmed; use alternatives that are suitable for pregnant women.
• Women with diabetes may be advised to use metformin with or without insulin during pregnancy
(and in the preconception period), when the likely benefits from improved blood glucose control
outweigh the potential for harm.[16]
• Stop all other oral blood glucose-lowering agents before and throughout pregnancy.[16]
Women who are breastfeeding can resume or continue metformin immediately after birth, but
should avoid other oral blood glucose-lowering therapy while breastfeeding.[16]
MANAGEMENT
• Stop ACE inhibitors and angiotensin-II receptor antagonists as soon as pregnancy is confirmed.[16]
• Stop SGLT2 inhibitors as soon as pregnancy is confirmed.[133]
• Stop statins as soon as pregnancy is confirmed.[16]
39
Women with diabetes who are breastfeeding should continue to avoid any medicines for their diabetes
complications that were stopped for safety reasons when they started planning the pregnancy.[16]
NICE recommends NPH insulin as the first choice for long-acting insulin during pregnancy.[16] Consider
continuing treatment with long-acting insulin analogues (insulin detemir or insulin glargine) for women with
diabetes who have established good blood glucose control while using these before pregnancy.[16]
• The available evidence on rapid-acting insulin analogues (insulin aspart and insulin lispro) does not
show an adverse effect on pregnancy or the health of the baby.[16]
• In practice, the majority of pregnant women with type 2 diabetes will need insulin.
Pregnant women should test their fasting, pre-meal, 1-hour post-meal, and bedtime blood glucose levels
every day.[16] The pattern should be examined every few weeks early in pregnancy so that nutrition
content and timing, exercise patterns, and the insulin doses can be modified to achieve optimal control.
Insulin requirements generally increase early in pregnancy, then decrease from about 8 to 16 weeks
before rising throughout the rest of the pregnancy.
Advise pregnant women with type 2 diabetes to take low-dose aspirin from 12 weeks until the birth of the
baby.[16] [195]
• These women are at high risk of pre-eclampsia.[195]
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial ( summary )
at initial diagnosis
1st lifestyle changes
plus agree glycaemic (HbA1c) target
adjunct blood pressure management
adjunct lipid management
adjunct antiplatelet therapy
adjunct add-on pharmacotherapy for patients with

CKD
with symptomatic plus insulin or sulfonylurea

hyperglycaemia
MANAGEMENT
Acute ( summary )
met formin tolerated and not
contraindicated: non-pregnant
HbA1c above goal 1st met formin
plus lifestyle measures, cardiovascular risk

reduction, and specific considerations for
CKD
HbA1c above goal on 1st met formin

met formin monotherapy
plus additional antihyperglycaemic agent

CKD
2nd met formin
plus additional two antihyperglycaemic agents

CKD
2nd insulin
adjunct SGLT2 inhibitor or GLP-1 receptor agonist

CKD
3rd bariatric surgery
met formin contraindicated or not

tolerated: non-pregnant
HbA1c above goal 1st DPP-4 inhibitor or pioglita zone or

sulfonylurea or SGLT2 inhibitor

CKD
HbA1c above goal on 1st dual therapy

monotherapy

CKD
MANAGEMENT
2nd insulin
41
Acute ( summary )
CKD
pregnant
1st low-dose aspirin
adjunct met formin
adjunct insulin
plus lifestyle measures and review medication

MANAGEMENT
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial
at initial diagnosis
1st lifestyle changes
» Diet and lifestyle are central to the

management of type 2 diabetes. Offer structured
education to the patient (and/or their family
members or carers) at and around the time
of diagnosis, with annual reinforcement and
review.[55]
» Ongoing self-management education by a

diabetes education nurse or dietitian promotes
diabetes self-care and supports beneficial
lifestyle changes.[55] [79] [80] [81] This requires
general nutrition and health lifestyle knowledge
and an individualised nutrition and exercise
plan based on an initial assessment and
treatment goals. Interventions that enhance self-
management can significantly reduce diabetes
distress.[82]
» Care of adults with type 2 diabetes must

include management of all major cardiovascular
risk factors to individualised targets. In addition
to glucose control, this includes smoking
cessation, blood pressure control (see Blood
pressure management), lipid control (see Lipid
management), consideration of antiplatelet use
for patients with high cardiovascular disease risk
(see Antiplatelet therapy), and ACE inhibitors
or angiotensin-II receptor antagonists - with
or without sodium-glucose co-transporter-2
(SGLT2) inhibitors - for patients with chronic
kidney disease or proteinuria (see Add-on
pharmacotherapy for patients with CKD).[42]
[55] [83] In addition, use of antihyperglycaemic
agents (glucagon-like peptide-1 [GLP-1]
receptor agonists SGLT2 inhibitors) that
reduce cardiovascular or overall mortality
or cardiovascular events may be especially
beneficial in those who have type 2 diabetes and
established cardiovascular disease regardless of
level of glucose management.[42] [84]
» If the patient smokes, give advice on smoking

MANAGEMENT
cessation and information on accessing smoking

cessation services.[55] [110] [111]
» Nutritional advice should be tailored to the

needs of the individual patient, and be provided
43
Initial
by a healthcare professional with specific
expertise and competencies in nutrition.[55]
» Encourage the patient to include high-fibre,

low-glycaemic-index sources of carbohydrate
in their diet (e.g., fruit, vegetables, wholegrains,
and pulses); eat low-fat dairy products and oily
fish; and limit their intake of foods containing
saturated and trans fatty acids.[55]
» Give individualised recommendations for

carbohydrate and alcohol intake, and meal
patterns. Reducing the risk of hypoglycaemia
should be a particular aim for a person using
insulin or an insulin secretagogue.[55] Although
limited substitution of sucrose-containing foods
for other carbohydrates in the meal plan is
allowable, advise the patient to take care to
avoid excess energy intake.[55] Discourage the
patient from eating food marketed specifically for
people with diabetes.[55]
» There is ongoing debate about the potential

role of low-carbohydrate diets in people with
type 2 diabetes.[42] Evidence suggests such
diets can be safe and effective in the short term
in managing weight, and improving glycaemic
control and cardiovascular risk.[92] One meta-
analysis found no difference in glucose-lowering
effects, weight, or low-density lipoprotein-
cholesterol levels between low- and high-
carbohydrate diets at 1 year or later.[93] Another
meta-analysis concluded there was moderate-
to low-quality evidence that some patients can
achieve remission of their type 2 diabetes by
following a low-carb diet for 6 months.[94]
» Integrate dietary advice with a personalised

diabetes management plan that includes other
aspects of lifestyle modification, including
increasing physical activity and losing weight.[95]
[96] [97] [98] [99]
» Encourage the patient to reduce

sedentary behaviour and be more physically
active.[96] Also encourage the patient to
incorporate activity into their daily life (e.g., brisk
walking, gardening, cycling).[96] [98] In this way,
the patient can gradually increase the amount
and intensity of activity they do.[96] Advise the
patient to do at least 30 minutes of moderate (or
greater intensity) physical activity on 5 or more
MANAGEMENT
days a week.[98]
» If the patient is overweight, set an initial body

weight loss target of 5% to 10%.[55] Evidence
suggests this is the minimum weight loss in
obese patients to improve glycaemic control,
Initial
lipid levels, and blood pressure.[42] Weight
loss management programmes with a healthy
eating and physical activity plan resulting in
an energy deficit have the potential for type 2
diabetes remission.[24] [100] [101] The Diabetes
Remission Clinical Trial (DiRECT) of supported
weight loss management for people diagnosed
with type 2 diabetes within the previous 6 years,
and a BMI of 27kg/m² to 45 kg/m², found that
almost half of participants achieved remission
to a non-diabetic state and were off antidiabetic
drugs at 12 months.[100] At 2 years, more than
one third of trial participants had sustained
remission.[102]
» An assessment of sleep duration and quality

should be considered. Obesity, diabetes,
hypertension, atrial fibrillation, and male sex are
risk factors for sleep apnoea, and inadequate
sleep may affect glycaemic control.[15]
plus agree glycaemic (HbA1c) target
Treatment recommended for ALL patients in
selected patient group
» HbA1c goals should be individualised at
all stages of management, according to the
needs and circumstances of your patient;
this is particularly important in the context of
multimorbidity.[55] Ensure the patient is involved
in any decisions about their individual glycaemic
target.[55]
» Individualised HbA1c goals improve quality of

life compared with uniform tight control.[117]
» In the UK, the National Institute for Health and

Care Excellence (NICE) recommends supporting
the patient to to aim for an HbA1c level of 48
mmol/mol (6.5%) if they manage their type 2
diabetes either with lifestyle and diet, or with
lifestyle and diet combined with a single drug not
associated with hypoglycaemia.[55] If the patient
is on a drug associated with hypoglycaemia,
support them to aim for an HbA1c level of 53
mmol/mol (7.0%).[55]
» Aim to make a routine assessment of frailty

whenever you review an older person with
diabetes.[58] [59] [60] Use a validated tool (e.g.,
the electronic Frailty Index [eFI], the Rockwood
frailty score, or Timed Up and Go) to confirm
MANAGEMENT
clinical suspicion of frailty.[59] [60] Frail patients

need a tailored approach to management.
Specifically bear in mind that glycaemic targets
recommended for good control in fit younger
people are too tight for frail older patients.[58]
[59] To determine the most appropriate HbA1c
45
Initial
target for your patient, check your local protocols
and consult a specialist if needed.
» Also consider a slightly higher HbA1c

level on a case-by-case basis for patients
who are unlikely to achieve longer-term risk-
reduction benefits (e.g., those with a reduced
life expectancy), those for whom intensive
management is not appropriate (e.g., people
with significant comorbidities), and people for
whom tight blood glucose control poses a high
risk of the consequences of hypoglycaemia,
including: people who are at risk of falling;
people who have impaired awareness of
hypoglycaemia; those who drive or operate
machinery as part of their job.[95]
» If the patient drives, ensure they are aware

of the relevant local advice on plasma glucose
level. In the UK, the Driver and Vehicle Licensing
Agency advises to aim for a level of at least 5
mmol/L (90 mg/dL) before driving.[119]
» Regular self-monitoring of blood glucose

(SMBG; finger stick blood glucose testing) may
help with self-management and medication
adjustment, particularly in people taking insulin.
SMBG can give insight into the impact of lifestyle
and medication management on blood glucose
and symptoms, particularly when combined with
education and support; SMBG plans should be
individualised.[120]
» NICE and the European Association for

the Study of Diabetes/American Diabetes
Association recommend SMBG as an option
for people with type 2 diabetes who are using
insulin.[55] [120] NICE also recommends
routinely offering SMBG for adults with type 2
diabetes if there is evidence of hypoglycaemic
episodes, or the patient is on oral medication
that may increase their risk of hypoglycaemia
while driving or operating machinery, or the
patient is pregnant or is planning to become
pregnant.[55] NICE recommends considering
short-term SMBG in adults with type 2 diabetes
(and reviewing treatment as necessary) when
starting treatment with oral or intravenous
corticosteroids, or to confirm suspected
hypoglycaemia.[55]
» Novel technologies, such as continuous

MANAGEMENT
or flash glucose monitoring, provide more

information than SMBG. However, continuous
or flash glucose monitoring might not be readily
available in all regions for people with type 2
diabetes.
Initial
» In practice, unless directed otherwise by
a specific clinical need or dosing regimen,
allow 3 to 6 months to assess the impact of
any intervention aimed at improving glycaemic
control, whether pharmacological or non-
pharmacological. Bear in mind that this
timeframe will vary on an individual patient
basis; carefully consider how much of a risk the
patient’s HbA1c might pose and step up to more
intense interventions more quickly if needed.
» If the patient is unable to meet their

individualised HbA1c goal with lifestyle
interventions, pharmacotherapy is recommended
to reduce risk of both microvascular
(nephropathy, retinopathy, neuropathy) and
macrovascular (myocardial infarction, stroke,
peripheral vascular disease) complications.[121]
[122] See the Acute timeframe.
adjunct blood pressure management
Treatment recommended for SOME patients in
» Consult your local protocols. Guidelines differ
regarding recommended blood pressure (BP)
targets for those with type 2 diabetes. The
prevalence of hypertension is >60% in patients
with type 2 diabetes.[42] Optimal BP control
reduces the risk of both microvascular and
macrovascular complications.[42]
» The National Institute for Health and Care

Excellence (NICE) in the UK recommends
maintaining blood pressure below 135/85 mmHg
for adults aged under 80, based on ambulatory
or home BP monitoring (or <140/90 mmHg
based on clinic BP).[57] Blood pressure should
be maintained below 145/85 mmHg for patients
aged 80 and over, based on ambulatory or home
BP monitoring (or <150/90 mmHg based on
clinic BP).[57]
» The NICE guideline committee concluded

that there was no evidence to suggest blood
pressure targets should be different in people
with type 2 diabetes; these recommendations for
blood pressure targets apply to people with and
without type 2 diabetes.[57] NICE also highlights
the importance of measuring standing as well
as sitting blood pressure in people with type 2
diabetes, based on expert opinion that this group
MANAGEMENT
of patients is at higher than usual risk of postural

hypotension.[57]
» The European Society of Cardiology (ESC)/

European Association for the Study of Diabetes
(EASD) guideline recommends a target systolic
47
Initial
BP (SBP) in people with diabetes up to the
age of 65 of 130 mmHg, and <130 mmHg if
tolerated (but no lower than 120 mmHg).[42] In
older people (aged >65 years), ESC/EASD
recommends SBP targeted to a range of 130
to 139 mmHg and a diastolic BP target of <80
mmHg (but not lower than 70 mmHg).[42]
» Regardless of the specific blood pressure

goal, both lifestyle changes and antihypertensive
medication may be needed to achieve BP
control. Reduced sodium intake (to <100 mmol/
day) and high intake of fruit, vegetables, and
low-fat dairy products have all been shown to
improve BP control.[42]
» Specific drug regimens for the management

of hypertension are beyond the scope of this
topic. Consult local protocols or guidelines for
guidance on drug and dose selection.
» In the UK, NICE recommends a stepwise

approach to pharmacological treatment of
hypertension in people without CKD.[57]
» Step 1: for initial treatment, give an ACE

inhibitor or an angiotensin-II receptor antagonist.
If an ACE inhibitor is not tolerated, use an
angiotensin-II receptor antagonist instead.
Do not combine an ACE inhibitor with an
angiotensin-II receptor antagonist. Use an
angiotensin-II receptor antagonist in preference
to an ACE inhibitor if the patient is of black
African or African–Caribbean family origin.[57]
» Step 2: if hypertension remains uncontrolled

on first-line therapies, discuss, and support,
adherence with antihypertensive medication. At
the same time, step up to dual therapy, offering
the choice of either a calcium-channel blocker
or a thiazide-like diuretic in addition to step 1
treatment.[57]
» Step 3: before considering next step treatment,

discuss adherence with the patient and
review their medications to ensure these
are being taken at optimal tolerated doses.
If the patient’s blood pressure remains
uncontrolled despite step 2 therapies, offer a
triple therapy combination of: an ACE inhibitor
or an angiotensin-II receptor antagonist, and
a calcium-channel blocker, and a thiazide-like
MANAGEMENT
diuretic.[57]
» Step 4: if blood pressure is not controlled

despite optimal tolerated doses of the triple-
therapy medications in step 3, regard the patient
Initial
as having resistant hypertension. Refer these
patients to a hypertension specialist.[57]
» If the patient has CKD and requires an

antihypertensive agent, an angiotensin-II
receptor antagonist or ACE inhibitor may be
the preferred option. Follow NICE guidelines
on chronic kidney disease (see Add-on
pharmacotherapy for patients with CKD). Where
possible, treat hypertension with drugs taken
only once a day.[57]
» The ESC/EASD guideline takes a broadly

similar approach to NICE but highlights
additional key messages.[42] It states that
there is strong evidence to support the use
of an ACE inhibitor or angiotensin-II receptor
antagonist, particularly in patients who have
microalbuminuria, proteinuria, or left ventricular
hypertrophy; these drugs have renoprotective
properties that go beyond their antihypertensive
effects alone.[42] The ESC/EASD recommends
dual therapy as first-line treatment because
most patients will not achieve BP control on a
single antihypertensive medication.[42] Use of
beta-blockers is not routinely recommended
by the ESC/EASD in patients with type 2
diabetes.[42] In practice, beta-blockers may
be considered if there are other compelling
indications (e.g., coronary artery disease, atrial
fibrillation, systolic heart failure).
» There is an increasing drive to incorporate the

use of home blood pressure monitoring into the
diagnosis and management of hypertension in
adults, including those with diabetes.[57] [103]
adjunct lipid management
» Consult your local protocols. Guidelines
recommend differing approaches to lipid-
modification therapy.
» In the UK, the National Institute for Health and

Care Excellence (NICE) and NHS England’s
Accelerated Access Collaborative (NHSE AAC)
recommend using a validated risk assessment
tool such as QRISK to assess cardiovascular
disease (CVD) risk in people with type 2
diabetes.[104] [105] [QRISK calculator] (https://
MANAGEMENT
qrisk.org/three)
» Use high-intensity statin treatment for the

primary prevention of CVD for people with
type 2 diabetes who have ≥10% 10-year
risk (estimated using QRISK) of developing
49
Initial
CVD.[104] [105] Before starting lipid-modification
therapy for the primary prevention of CVD,
take at least one lipid sample to measure a full
lipid profile. This should include measurement
of total cholesterol, high-density lipoprotein
(HDL)-cholesterol, non-HDL-cholesterol, and
triglyceride concentrations. A fasting sample
is not needed.[104] [105] The higher end of
the dose range of a high-intensity statin is
recommended for secondary prevention if the
patient has established CVD (provided they have
normal renal function).[104] [105]
» Consistent data have demonstrated the

efficacy of statins in preventing cardiovascular
events and reducing cardiovascular mortality in
patients with diabetes, with no evidence for sex
differences; their use is associated with a limited
number of adverse events.[42]
» In terms of monitoring, NICE and the NHSE

AAC recommend measuring total cholesterol,
HDL-cholesterol, and non-HDL-cholesterol in all
people who have been started on high-intensity
statin treatment at 3 months of treatment and
aiming for a greater than 40% reduction in
non-HDL-cholesterol. Arrange for specialist
assessment of people with a total cholesterol
concentration of more than 9.0 mmol/L (347.5
mg/dL) or a non-HDL-cholesterol concentration
of more than 7.5 mmol/L (290 mg/dL) even in
the absence of a first-degree family history of
premature coronary heart disease.[104] [105] If
a greater than 40% reduction in non-HDL-
cholesterol is not achieved, discuss adherence
and timing of dose, optimise adherence to diet
and lifestyle measures, and consider increasing
the statin dose if the person is judged to be
at higher risk because of comorbidities or risk
score, or based on clinical judgement.[104]
[105] NICE and the NHSE AAC recommend
reviewing medication annually. Use these
reviews to discuss medication adherence and
lifestyle modification and to address CVD
risk factors. Consider an annual non-fasting
blood test for non-HDL-cholesterol to inform
the discussion.[104] [105] Do not stop statins
because of an increase in blood glucose level or
HbA1c.[104] [105]
» NICE recommends seeking specialist advice

about suitable options for treating people with
MANAGEMENT
type 2 diabetes who are intolerant to three

different statins.[104]
» The European Society of Cardiology

(ESC)/European Association for the Study of
Diabetes (EASD) guidelines categorise patients
Initial
with diabetes according to cardiovascular
risk.[42] Based on these categories, the ESC
recommends in patients with type 2 diabetes
who are at moderate cardiovascular risk: a low-
density lipoprotein (LDL)-cholesterol target of
<2.6 mmol/L (<100 mg/dL).[42] For patients
who are at high cardiovascular risk, the ESC
recommends an LDL-cholesterol target of
<1.8 mmol/L (<70 mg/dL) and LDL-cholesterol
reduction of at least 50%, and a secondary
goal of a non-HDL-cholesterol target of <2.6
mmol/L (<100 mg/dL).[42] For those at very
high cardiovascular risk, the ESC recommends
an LDL-cholesterol target of <1.4 mmol/L (<55
mg/dL) and LDL-cholesterol reduction of at
least 50%, and a secondary goal of a non-HDL-
cholesterol target of <2.2 mmol/L (<85 mg/
dL).[42]
» The ESC recommends statins as first-line

lipid-lowering treatment in patients with diabetes
and high LDL-cholesterol levels.[42] The
cardiovascular risk profile (very high, high,
moderate) of the individual patient and the
corresponding LDL-cholesterol (or non-HDL-
cholesterol) target levels should be used to
determine statin administration.[42] If the
recommended target LDL-cholesterol is not
reached, consider intensifying lipid-lowering
therapy on an individual basis.[42]
» For some patients with diabetes and

established coronary heart disease who have
persistently elevated LDL despite maximally-
tolerated statin therapy, addition of ezetimibe or
a proprotein convertase subtilisin/kexin type 9
(PCSK9) inhibitor (e.g., alirocumab, evolocumab)
may confer clinical benefit.[42] [106] [107]
[108] In addition, newer lipid-lowering therapies,
such as bempedoic acid, may be considered
for lipid lowering, in combination with either a
statin or with a statin and other lipid-lowering
therapies (e.g., ezetimibe). Bempedoic acid
can also be considered alone or in combination
with other lipid-lowering therapies in people
who are statin-intolerant or for whom a statin is
contraindicated.[109]
» Specific drug regimens for the management

of hyperlipidaemia are beyond the scope of this
topic. Consult local protocols or guidelines for
guidance on drug and dose selection.
MANAGEMENT
adjunct antiplatelet therapy

51
Initial
Primary options
» aspirin: 75 mg orally once daily
Secondary options
» clopidogrel: 75 mg orally once daily
» People with type 2 diabetes and cardiovascular

disease (CVD) will need antiplatelet
monotherapy for secondary prevention. This
will usually be in the form of low-dose aspirin
or clopidogrel.[42] [112] Antiplatelet therapy
has been found to reduce the risk of stroke,
myocardial infarction, or vascular death.[113]
» The role of antiplatelets in primary prevention

of CVD is unclear and guidelines differ in their
recommendations.[42] Consult your local
protocols.
» The National Institute for Health and

Care Excellence in the UK recommends
against routine antiplatelet therapy (aspirin
or clopidogrel) for adults with type 2 diabetes
without cardiovascular disease.[55] This is
because the increased risk of major bleeding
is considered to outweigh any potential
benefits.[114] The ASCEND trial comparing low-
dose aspirin with placebo among 15,480 adults
with diabetes but no evident CVD found that
the benefits of aspirin use in preventing serious
vascular events was largely counterbalanced by
the increased risk of major bleeding events over
a mean follow-up of 7.4 years.[115]
» However, the European Society of Cardiology

(ESC)/European Association for the Study of
Diabetes (EASD) guideline recommends to
consider low-dose aspirin for primary prevention
of CVD in patients with diabetes who are at high/
very high risk of CVD, provided there are no
clear contraindications.[42] The ESC/EASD does
not recommend aspirin for primary prevention
in patients at mild-moderate risk of CVD (e.g.,
patients aged <50 years with type 2 diabetes
duration <10 years without other risk factors).[42]
» The ESC/EASD recommends to consider

concomitant use of a proton-pump inhibitor in
patients taking low-dose aspirin to reduce the
bleeding risk highlighted by the ASCEND trial (in
MANAGEMENT
which three-quarters of patients were not taking

a proton-pump inhibitor).[42]
adjunct add-on pharmacotherapy for patients with
CKD
Initial
» If your patient has chronic kidney disease
(CKD) or develops it at any point post-diagnosis,
NICE recommends to give an angiotensin-
II receptor antagonist or an ACE inhibitor
(titrated to the highest licensed dose that the
person can tolerate) if albumin-to-creatinine
ratio (ACR) is 3 mg/mmol or more.[55] [63]
Give an SGLT2 inhibitor (in addition to the
angiotensin-II receptor antagonist or ACE
inhibitor) if the patient is already taking an
angiotensin-II receptor antagonist or an ACE
inhibitor (titrated to the highest licensed dose
that they can tolerate), ACR is over 30 mg/
mmol, and the patient meets the criteria in the
marketing authorisation (including relevant
estimated glomerular filtration rate [eGFR]
thresholds).[55] Consider an SGLT2 inhibitor (in
addition to the angiotensin-II receptor antagonist
or ACE inhibitor) if the patient is already taking
an angiotensin-II receptor antagonist or an ACE
inhibitor (titrated to the highest licensed dose
that they can tolerate), ACR is between 3 and 30
mg/mmol, and the patient meets the criteria in
the marketing authorisation (including relevant
estimated glomerular filtration rate [eGFR]
thresholds).[55]
» If the patient has CKD and requires an

antihypertensive agent, also follow the
recommendations outlined here (instead of the
standard stepwise approach to blood pressure
management for people without CKD). Where
possible, treat hypertension with drugs taken
only once daily.[57]
» These drugs should be added to optimised

standard care (as outlined in the Acute
timeframe). In practice, if the patient has CKD
with eGFR >45 mL/minute/1.73 m², it may be
appropriate for them to take an SGLT2 inhibitor
for both antihyperglycaemic and renal benefit.
However, if the patient has CKD with eGFR
<45 mL/minute/1.73 m², the glucose-lowering
effects of SGLT2 inhibitors will be negligible
and therefore they will need an alternative
antihyperglycaemic agent for initial glucose-
lowering therapy.[133]
» SGLT2 inhibitors are not suitable for everyone

MANAGEMENT
and should only be used within their marketing

authorisation; some SGLT2 inhibitors are not
licensed for this indication in some regions,
including the UK.[55]
53
Initial
» These recommendations from NICE are based
on evidence from randomised controlled trials
(RCTs) which showed that SGLT2 inhibitors
reduce the risk of CKD progression, mortality
and cardiovascular events in adults with type 2
diabetes and CKD.[55] RCTs also showed that
angiotensin-II receptor antagonists reduce the
risk of end-stage renal disease and heart failure,
as well as no clear difference between ACE
inhibitors and angiotensin-II receptor antagonists
on a number of outcomes, including end-stage
renal disease, all-cause mortality, cardiovascular
mortality, and hospitalisation.[63]
with symptomatic plus insulin or sulfonylurea
hyperglycaemia
» If an adult with type 2 diabetes is
symptomatically hyperglycaemic at initial
diagnosis (or at any subsequent time during
treatment), consider rescue therapy with insulin
or a sulfonylurea, and review treatment when
blood glucose control has been achieved.[55]
» In practice, the first-line glucose-lowering

therapy for longer-term use (e.g., metformin;
see the Acute timeframe) is often introduced at
the same time so that it can start to take effect
sooner and rescue therapy can be withdrawn at
the earliest appropriate opportunity.
MANAGEMENT
Acute
met formin tolerated and not
contraindicated: non-pregnant
HbA1c above goal 1st met formin

Primary options
» metformin: 500 mg orally (immediate-

release) once daily for at least one week,
followed by 500 mg twice daily for at least
one week, then 500 mg three times daily
thereafter, maximum 2000 mg/day
Also available as a modified-release
formulation. If the immediate-release
formulation is not tolerated, consider a trial
of the modified-release formulation. National
Institute for Health and Care Excellence.
Type 2 diabetes in adults: management.
November 2021 [internet publication]. https://
www.nice.org.uk/guidance/ng28
» If HbA1c rises to 48 mmol/L (6.5%; or the

patient’s individualised goal) on lifestyle
interventions, the UK National Institute
for Health and Care Excellence (NICE)
recommends to give immediate-release
metformin as first-line therapy in the absence of
contraindications.[55] Always use an appropriate
HbA1c target for the individual patient. Metformin
is the recommended first choice because
of its safety profile, its likely cardiovascular
benefit, and the long-term experience in its
use.[121] [123] Metformin may be safely used
(with a possible dose reduction) in patients
with reduced estimated glomerular filtration
rates (eGFRs), but it is contraindicated if eGFR
<30 mL/minute/1.73 m².[15] [120] Review the
dose of metformin if the eGFR is below 45 mL/
minute/1.73 m².[55] Stop metformin if the eGFR
is below 30 mL/minute/1.73 m².[55] Prescribe
metformin with caution for those at risk of a
sudden deterioration in kidney function and
those at risk of eGFR falling below 45 mL/
minute/1.73 m².[55]
» The recommendations in this topic are

based primarily on NICE guidelines, which
are glucocentric in their approach, with
sodium-glucose co-transporter-2 (SGLT2)
inhibitors and glucagon-like peptide-1 (GLP-1)
receptor agonists generally only recommended
MANAGEMENT
as second-line options for people with

elevated glucose levels after metformin
treatment.[55] However, since the publication of
the NICE guideline, some treatment strategies
have shifted to a focus on the absolute reduction
55
Acute
of cardiovascular and kidney disease outcomes
instead of being led by glycaemic control.
In practice, therefore, monotherapy with an
SGLT inhibitor or a GLP-1 receptor agonist is
increasingly used as a first-line alternative to
metformin.[130] This is based on evidence from
high-quality randomised trials demonstrating
atherosclerotic cardiovascular disease
(CVD) and chronic kidney disease benefits
independent of medications’ glucose-lowering
potential.[129] In particular, SGLT2 inhibitors
appear to have benefits in patients with type 2
diabetes who have more than three risk factors
for CVD, and both SGLT2 inhibitors and GLP-1
receptor agonists appear beneficial in those
with established CVD and/or renal disease.[125]
[128] [130] [BMJ: SGLT-2 inhibitors or GLP-1
receptor agonists for adults with type 2 diabetes]
(https://www.bmj.com/content/373/bmj.n1091)
NICE updated its guideline in November 2021 to
recognise a separate role for SGLT2 inhibitors -
regardless of glycaemic control - for patients with
CKD whose albumin-to-creatinine ratio is above
a specified level despite treatment with an ACE
inhibitor or angiotensin-II receptor antagonist.
See Add-on pharmacotherapy for patients with
CKD in the Initial timeframe.
» A 2019 update to a joint consensus report

from the American Diabetes Association (ADA)
and the European Association for the Study
of Diabetes (EASD) recommends that if a
patient with type 2 diabetes has established
CVD, there is a compelling indication for
treatment with a GLP-1 receptor agonist or
SGLT2 inhibitor.[129] The ADA/EASD also
recommend, if a patient with type 2 diabetes
is at high risk of CVD, considering treatment
with a GLP-1 receptor agonist or SGLT2
inhibitor independently of their baseline HbA1c
or individualised HbA1c target with the aim
of reducing major cardiovascular events or
death and slowing progression of kidney
impairment.[129]
» There is a risk for euglycaemic diabetic

ketoacidosis with all SGLT2 inhibitors.[49]
[170] [171] The UK Medicines and Healthcare
products Regulatory Agency (MHRA) and
the European Medicines Agency warn of
an increased risk of lower-limb amputation
MANAGEMENT
(mainly toes) in patients with type 2 diabetes

taking canagliflozin.[172] [173] This was based
on findings from the CANVAS trials.[142]
[148] [149] However, this was not seen in the
subsequent CREDENCE trial.[146] The MHRA
emphasises the importance of preventive foot
Acute
care for all patients with diabetes.[174] The ADA/
EASD recommends that patients with foot ulcers
or at high risk for amputation should only be
treated with SGLT2 inhibitors after careful shared
decision-making around risks and benefits with
comprehensive education on foot care and
amputation prevention.[129] Evidence does
not show an increased risk for dapagliflozin
and empagliflozin, but the risk may be a
class effect. The MHRA and the US Food
and Drug Administration warn of cases of
necrotising fasciitis of the perineum (also known
as Fournier's gangrene) observed in post-
marketing surveillance of SGLT2 inhibitors.[175]
[176] Thus, SGLT2 inhibitors should be avoided
in patients with conditions that increase the risk
for limb amputations, and in patients prone to
urinary tract or genital infections.
CKD
review.[55] Ongoing self-management education
by a diabetes education nurse or dietitian
promotes diabetes self-care and supports
beneficial lifestyle changes.[55] [79] [80]
[81] This requires general nutrition and health
lifestyle knowledge and an individualised
nutrition and exercise plan based on an initial
assessment and treatment goals. Interventions
that enhance self-management can significantly
reduce diabetes distress.[82]

risk factors to individualised targets. In
addition to glucose control, this includes
smoking cessation, blood pressure control,
lipid control, antiplatelet use for patients
with high cardiovascular disease risk, and
ACE inhibitors or angiotensin-II receptor
antagonists - with or without sodium-glucose co-
transporter-2 (SGLT2) inhibitors - for patients
with chronic kidney disease or proteinuria.[42]
MANAGEMENT

receptor agonists and SGLT2 inhibitors) that
57
Acute
» For more detail on lifestyle measures,

cardiovascular risk reduction, and
pharmacological considerations for people with
CKD, see the Initial timeframe.
HbA1c above goal on 1st met formin
met formin monotherapy
Primary options

» If HbA1c rises to the patient’s agreed threshold

for intensification (typically 58 mmol/mol [7.5%]
but may be individualised according to the
patient’s circumstances) despite initial drug
treatment with metformin monotherapy, the UK
National Institute for Health and Care Excellence
recommends to consider dual therapy including
metformin.[55]
» Suitable options are: metformin and a

dipeptidyl peptidase-4 (DPP-4) inhibitor;
metformin and pioglitazone (a thiazolidinedione);
metformin and a sulfonylurea.[55] See Additional
antihyperglycaemic agent.
» Support the patient to aim for an HbA1c level

of 53 mmol/mol (7.0%).[55]
plus additional antihyperglycaemic agent
Primary options
DPP-4 inhibitor
» alogliptin: 25 mg orally once daily
MANAGEMENT
OR
DPP-4 inhibitor
» linagliptin: 5 mg orally once daily
Acute
OR
DPP-4 inhibitor
» saxagliptin: 5 mg orally once daily
OR
DPP-4 inhibitor
» sitagliptin: 100 mg orally once daily
OR
Thia zolidinedione
» pioglitazone: 15-30 mg orally once daily
initially, adjust dose according to response,
maximum 45 mg/day
OR
Sulfonylurea
» gliclazide: 40-80 mg orally (immediate-
release) once daily initially, adjust dose
according to response, maximum 320 mg/
day; 30 mg orally (modified-release) once
daily initially, adjust dose according to
response, maximum 120 mg/day
Doses >160 mg/day (immediate-release)
should be given in divided doses.
OR
Sulfonylurea
» glimepiride: 1 mg orally once daily initially,
adjust dose according to response, maximum
4-6 mg/day
OR
SGLT2 inhibitor
» canagliflozin: 100 mg orally once daily
maximum 300 mg/day
OR
SGLT2 inhibitor
» dapagliflozin: 10 mg orally once daily
OR
MANAGEMENT
SGLT2 inhibitor
» empagliflozin: 10 mg orally once daily
maximum 25 mg/day
59
Acute
Not recommended in adults ≥85 years of age.
OR
SGLT2 inhibitor
» ertugliflozin: 5 mg orally once daily initially,
15 mg/day
OR
GLP-1 receptor agonist

» dulaglutide: 1.5 mg subcutaneously once
weekly initially for at least 4 weeks, adjust
dose according to response, maximum 4.5
mg/week
OR

» exenatide: 5 micrograms subcutaneously
(immediate-release) twice daily initially for
at least 1 month, adjust dose according to
response, maximum 20 micrograms/day; 2
mg subcutaneously (modified-release) once
weekly
OR

» liraglutide: 0.6 mg subcutaneously once
daily initially for at least 1 week, adjust dose
according to response, maximum 1.8 mg/day
OR

» lixisenatide: 10 micrograms subcutaneously
once daily initially for 2 weeks, adjust
dose according to response, maximum 20
micrograms/day
OR

» semaglutide: 0.25 mg subcutaneously
once weekly initially for 4 weeks, adjust dose
according to response, maximum 1 mg/week;
3 mg orally once daily initially for 1 month,
MANAGEMENT

14 mg/day
Important - the subcutaneous formulation is
given once weekly, while the oral formulation
is given once daily.
Acute
» If HbA1c rises to the patient’s agreed threshold
for intensification (typically 58 mmol/mol [7.5%]
but may be individualised according to the
patient’s circumstances) despite initial drug
treatment, the UK National Institute for Health
and Care Excellence (NICE) recommends to
support the patient to aim for an HbA1c level of
53 mmol/mol (7.0%) and consider dual therapy.
Suitable options are: metformin and a dipeptidyl
peptidase-4 (DPP-4) inhibitor; metformin and
pioglitazone (a thiazolidinedione); metformin and
a sulfonylurea.[55]
» Combination treatment with metformin and

a sodium-glucose co-transporter-2 (SGLT2)
inhibitor may be appropriate in some patients
with type 2 diabetes (e.g., a sulfonylurea is
contraindicated or not tolerated, the person
is at significant risk of hypoglycaemia or its
consequences). In these situations, NICE
recommends to consider the following options:
metformin and canagliflozin; metformin and
dapagliflozin; metformin and empagliflozin; or
metformin and ertugliflozin.[55] [132] [134] [135]
[136]
» If your patient does not have established

cardiovascular disease (CVD), choose an
agent to combine with metformin according
to individual patient needs.[137] To avoid
hypoglycaemia: use a DPP-4 inhibitor or
pioglitazone or an SGLT2 inhibitor.[137] For
rapid glycaemic response, or if the patient is
on corticosteroids: choose a sulfonylurea or
insulin (ongoing or rescue therapy).[137] For
weight loss: an SGLT2 inhibitor is most
appropriate.[137] In frail/older patients:
use a DPP-4 inhibitor; avoid drugs causing
hypoglycaemia and SGLT2 inhibitors.[137] If
all factors are equal: choose pioglitazone or a
sulfonylurea.[137]
» Bear in mind that SGLT inhibitors have minimal

glycaemic benefit if eGFR <45 mL/minute/1.73
m² (as might be the case if the patient has
CKD).[133]
» If the patient has established atherosclerotic

CVD, the European Society of Cardiology/
recommends dual therapy of metformin with
either: an SGLT2 inhibitor with CVD benefits
MANAGEMENT
(strongest evidence is for dapagliflozin,

canagliflozin, and empagliflozin), or a glucagon-
like peptide-1 (GLP-1) receptor agonist with CVD
benefits (strongest evidence for cardiovascular
mortality benefit is for liraglutide; semglutide
and dulaglutide have also been shown to reduce
61
Acute
cardiovascular events in patients with diabetes
and CVD, and in those who are at very high/high
cardiovascular risk).[42]

care for all patients with diabetes.[174] The
American Diabetes Association/European
Association for the Study of Diabetes
recommends that patients with foot ulcers
» NICE is in the process of updating

its recommendations on choice of first
intensification medication after its evidence
review highlighted the importance of
comorbidities including CVD, heart failure,
and chronic kidney disease in informing the
most beneficial choice of medication for the
patient.[138]
» Bear in mind that drugs in dual therapy should

be introduced in a stepwise manner, checking for
» Dose adjustments may be required when

using combinations of these drugs. Lower
MANAGEMENT
doses of certain drugs (e.g., a sulfonylurea,

insulin) may be required in order to reduce the
risk of hypoglycaemia. Consult your local drug
formulary for more information.
Acute
» These drugs may be available in proprietary
fixed-dose combination formulations with
metformin to aid patient adherence. Consult your
local drug formulary for more information.
CKD


cardiovascular risk reduction and
MANAGEMENT
2nd met formin

Primary options

63
Acute
» If, despite dual therapy with metformin and

another oral drug, HbA1c rises to the patient’s
agreed threshold for intensification (typically
58 mmol/mol [7.5%] but may be individualised
according to the patient’s circumstances),
the UK National Institute for Health and Care
Excellence recommends to consider either
triple therapy (i.e., metformin, a dipeptidyl
peptidase-4 [DPP-4] inhibitor, and a sulfonylurea;
or metformin, pioglitazone, and a sulfonylurea;
or metformin, pioglitazone or a sulfonylurea,
and a sodium-glucose co-transporter-2 [SGLT2]
inhibitor [see Additional two antihyperglycaemic
agents]), or starting insulin-based treatment (see
2nd line: insulin).[55]
plus additional two antihyperglycaemic agents
Primary options
DPP-4 inhibitor plus a sulfonylurea
-or-
-or-
-or-
--AND--
-or-
MANAGEMENT

4-6 mg/day
OR
Acute
Thia zolidinedione plus a sulfonylurea
maximum 45 mg/day
--AND--
-or-
4-6 mg/day
OR
Thia zolidinedione or a sulfonylurea plus

a SGLT2 inhibitor
maximum 45 mg/day
-or-
-or-
4-6 mg/day
--AND--
maximum 300 mg/day
-or-
-or-
maximum 25 mg/day
MANAGEMENT
-or-
15 mg/day
Secondary options
65
Acute
Sulfonylurea plus a GLP-1 receptor
agonist
-or-
4-6 mg/day
--AND--
mg/week
-or-
weekly
-or-
-or-
micrograms/day
-or-
14 mg/day

MANAGEMENT

Excellence recommends to support the patient
to aim for an HbA1c level of 53 mmol/mol
(7.0%) and consider either triple therapy (i.e.,
metformin, a dipeptidyl peptidase-4 [DPP-4]
Acute
inhibitor, and a sulfonylurea; or metformin,
pioglitazone, and a sulfonylurea; or metformin,
pioglitazone or a sulfonylurea, and a sodium-
glucose co-transporter-2 [SGLT2] inhibitor), or
starting insulin-based treatment.[55]
» If this approach is not effective, not tolerated,

or contraindicated, consider combination
therapy with metformin, a sulfonylurea, and
a glucagon-like peptide-1 (GLP-1) receptor
agonist for adults with type 2 diabetes who
have a body mass index (BMI) of 35 kg/m²
or higher (adjust accordingly for people from
black, Asian, and other minority ethnic groups)
and specific psychological or other medical
problems associated with obesity.[55] Also
consider combination therapy with metformin,
a sulfonylurea, and a GLP-1 receptor agonist
for the patient with a BMI lower than 35 kg/
m² and for whom insulin therapy would have
significant occupational implications or weight
loss would benefit other significant obesity-
related comorbidities.[55]
» Only continue GLP-1 receptor agonist therapy

if the patient has had a beneficial metabolic
response (a reduction of at least 11 mmol/mol
[1.0%] in HbA1c and a weight loss of at least 3%
of initial body weight in 6 months).[55]
» Bear in mind that SGLT inhibitors have minimal

glycaemic benefit if eGFR <45 mL/minute/1.73
m² (as might be the case if the patient has
CKD).[133]

MANAGEMENT

67
Acute

CKD

MANAGEMENT

Acute
2nd insulin
Primary options
» insulin isophane human (NPH)
OR
» insulin detemir
OR
» insulin glargine
OR

-or-
» insulin detemir
-or-
» insulin glargine
--AND--
» insulin lispro
-or-
» insulin aspart
-or-
» insulin glulisine

Excellence (NICE) recommends to support the
patient to aim for an HbA1c level of 53 mmol/mol
(7.0%) and consider either starting insulin-based
treatment, or triple therapy.[55]
» When starting insulin therapy, the patient

should continue metformin as long as there are
no contraindications or intolerances. Review the
continued need for other blood glucose-lowering
therapies.[55]
» NICE recommends choosing the most

MANAGEMENT
appropriate insulin type and individualised

regimen based on individual patient
circumstances.[55] Give basal isophane (NPH)
insulin injected once or twice daily according to
need.[55] Consider starting both NPH and short-
acting insulin (particularly if the person's HbA1c
69
Acute
is 75 mmol/mol [9.0%] or higher), administered
either separately or as a pre-mixed (biphasic)
human insulin preparation.[55] Consider
using insulin detemir or insulin glargine as
an alternative to NPH insulin if: the patient
needs assistance from a carer or healthcare
professional to inject insulin, and use of insulin
detemir or insulin glargine would reduce the
frequency of injections from twice to once
daily; or the patient’s lifestyle is restricted by
recurrent symptomatic hypoglycaemic episodes;
or they would otherwise need twice-daily NPH
insulin injections in combination with oral
glucose-lowering drugs.[55] Consider pre-
mixed (biphasic) preparations that include short-
acting insulin analogues, rather than pre-mixed
(biphasic) preparations that include short-acting
human insulin preparations, if: the patient prefers
injecting insulin immediately before a meal; or
hypoglycaemia is a problem; or blood glucose
levels rise markedly after meals.[55]
» Consider switching to insulin detemir or insulin

glargine from NPH insulin if the patient does not
reach their target HbA1c because of significant
hypoglycaemia or experiences significant
hypoglycaemia on NPH insulin irrespective
of the level of HbA1c reached.[55] Also
consider switching if the patient cannot use
the device needed to inject NPH insulin but
could administer their own insulin safely and
accurately if switched to one of the long-acting
insulin analogues or needs help from a carer
or healthcare professional to administer insulin
injections and for whom switching to one of the
long-acting insulin analogues would reduce the
number of daily injections.
» If the patient is on a basal insulin regimen

(NPH insulin, insulin detemir, or insulin glargine),
monitor for the need for short-acting insulin
before meals (or a pre-mixed [biphasic] insulin
preparation).[55]
» If the patient is on pre-mixed (biphasic) insulin,

monitor for the need for a further injection of
short-acting insulin before meals or for a change
to a basal bolus regimen with NPH insulin
or insulin detemir or insulin glargine, if blood
glucose control remains inadequate.[55]
» Most people with type 2 diabetes will use

MANAGEMENT
insulin delivery devices (insulin pens). These can

be adjusted to administer set doses of insulin,
are widely available, and offer convenience
and accuracy in insulin dosing. Less frequently,
insulin pumps and patch pump systems are
used on a case-by-case basis in people who
Acute
need multiple daily dose insulin. Insulin pumps
are typically reserved for people with type 1
diabetes. If an insulin pump is appropriate for
the patient, its use will require significant patient
engagement to achieve clinical benefits beyond
multiple daily dose injection-based therapy.
» Exogenous insulin is a very effective way to

lower serum glucose and lower HbA1c, but its
use must be guided in most patients by regular
self-monitored blood glucose testing (finger stick
blood glucose testing) or continuous glucose
monitoring.
» Hypoglycaemia (glucose ≤3.9 mmol/L

[≤70 mg/dL]) is the most serious potential
complication of insulin therapy. People who
drive need to be particularly careful to avoid
hypoglycaemia and should be warned of the
dangers. See Complications. Another significant
side effect is weight gain. Less common side
effects may include hunger, nausea, diaphoresis,
injection site irritation, or anaphylaxis.
» When basal-bolus insulin is used by motivated

and knowledgeable patients, the dose of rapid-
acting insulin that is administered before each
meal can be based on anticipated carbohydrate
content of the upcoming meal and sometimes
adjusted for anticipated physical activity.
» A correction (or adjustment) dose may be

added to the bolus insulin based on the pre-meal
blood glucose level. In practice, a conservative
approach to calculating a correction dose is to
assume 1 unit of insulin will lower the patient’s
blood glucose by 2 to 4 mmol/L (36-72 mg/
dL). Correction dosing can also be calculated
using the patient's total daily dose of insulin
if food intake is stable. The correction dose
can be added to the patient's mealtime insulin
requirement (whether based on general meal
size or carbohydrate counting) and given as the
total bolus dose.
» Various pre-mixed (biphasic) insulin

formulations are available; consult your local
drug formulary for options.
MANAGEMENT
Primary options
SGLT2 inhibitor
71
Acute
maximum 300 mg/day
OR
SGLT2 inhibitor
OR
SGLT2 inhibitor
maximum 25 mg/day
OR
SGLT2 inhibitor
15 mg/day
OR

mg/week
OR

weekly
OR

MANAGEMENT
OR

Acute
micrograms/day
OR

14 mg/day
» The UK National Institute for Health and Care

Excellence recommends considering a sodium-
glucose co-transporter-2 (SGLT2) inhibitor or
glucagon-like peptide-1 (GLP-1) receptor agonist
in combination with insulin, with or without other
antidiabetic drugs.[55]

MANAGEMENT

73
Acute
» Only offer a GLP-1 receptor agonist in
combination with insulin with specialist care
advice and ongoing support from a consultant-
led multidisciplinary team.[55] The MHRA warns
of cases of diabetic ketoacidosis in patients
with type 2 diabetes on a combination of a
GLP-1 receptor agonist and insulin who had
doses of concomitant insulin rapidly reduced or
discontinued.[140]
» Lower doses of insulin may be required when

these drugs are added on to insulin in order to
reduce the risk of hypoglycaemia. Consult your
CKD

MANAGEMENT

Acute
» Guidelines from the National Institute

for Health and Care Excellence in the UK
recommend offering an expedited assessment
for bariatric surgery to anyone with a body mass
index (BMI) of 35 or over who has recent-onset
type 2 diabetes (diagnosis within last 10 years)
as long as they are also receiving or will receive
assessment by a clinician-led community-
based multidisciplinary team (a ‘tier 3’ service
in the UK).[98] Consider an assessment for
bariatric surgery for anyone with a BMI of 30
to 34.9 kg/m² who has recent-onset type 2
diabetes as long as they are also receiving or
will receive assessment in a ‘tier 3’ service (or
equivalent).[98] Consider an assessment for
bariatric surgery for anyone of Asian family origin
who has recent-onset type 2 diabetes at a lower
BMI than other populations as long as they are
also receiving or will receive assessment in a
‘tier 3’ service (or equivalent).[98] People of
Asian family origin have comorbidity risk factors
that are of concern at lower BMIs.
» The 2018 American Diabetes Association/

consensus guideline recommends bariatric
surgery as an option for patients with type 2
diabetes who have: a BMI ≥ 40.0 kg/m² if of non-
Asian ancestry; a BMI ≥ 37.5 kg/m² if of Asian
ancestry; a BMI of 35.0 to 39.9 kg/m² (32.5 to
37.4 kg/m² if of Asian ancestry) and who cannot
achieve durable weight loss with non-surgical
methods.[120]
» Randomised clinical trials have shown a

benefit from bariatric surgery (also referred to
as metabolic surgery) compared with medical
therapy alone with regard to diabetes remission,
glycaemic control, need for glucose-lowering
medications, quality of life, and reduction in
cardiovascular risk factor markers over the
short term (e.g., 1-3 years) in people with type
2 diabetes, as well as for possible prevention
of type 2 diabetes.[184] [185] [186] [187]
[188] [189] Cohort studies suggest that both
MANAGEMENT
Roux en Y bypass and sleeve gastrectomy

procedures lead to diabetes remission that
lasts a mean of about 5 years in more than half
of patients, and significantly reduce mortality,
stroke, myocardial infarction, and microvascular
complications in those with type 2 diabetes.[190]
75
Acute
[191] [192] Compared with sleeve gastrectomy,
Roux en Y leads to somewhat greater weight
loss and other benefits, but is a more technically
challenging operation with higher re-operation
and readmission rates. The benefits and risks
of bariatric surgery also vary substantially
across type 2 diabetes patient subgroups.
In observational studies, average benefits
appear to be highest in people with more
recent onset of type 2 diabetes, and those not
on insulin therapy.[172] [193] Benefits have
been documented in younger people (age
40-50 years) as well as those over 65 years of
age.[172] [193]
met formin contraindicated or not
tolerated: non-pregnant
HbA1c above goal 1st DPP-4 inhibitor or pioglita zone or

sulfonylurea or SGLT2 inhibitor
Primary options
DPP-4 inhibitor
OR
DPP-4 inhibitor
OR
DPP-4 inhibitor
OR
DPP-4 inhibitor
OR
Thia zolidinedione
maximum 45 mg/day
OR
MANAGEMENT
Sulfonylurea
Acute
OR
Sulfonylurea
4-6 mg/day
Secondary options
SGLT2 inhibitor
maximum 300 mg/day
OR
SGLT2 inhibitor
OR
SGLT2 inhibitor
maximum 25 mg/day
OR
SGLT2 inhibitor
15 mg/day
» If metformin is contraindicated or not tolerated,

consider initial drug treatment with a dipeptidyl
peptidase-4 (DPP-4) inhibitor, or pioglitazone (a
thiazolidinedione), or a sulfonylurea.[55]
» Pioglitazone is not a suitable option if

the patient has any of: heart failure or
history of heart failure; hepatic impairment;
diabetic ketoacidosis; current, or a history of,
bladder cancer; uninvestigated macroscopic
haematuria.[55]
MANAGEMENT

monotherapy with a sodium-glucose co-
transporter-2 (SGLT2) inhibitor as an option for
patients in whom metformin is contraindicated
77
Acute
or not tolerated, when diet and exercise alone
do not provide adequate glycaemic control, and
only if a DPP-4 inhibitor would otherwise be
prescribed and a sulfonylurea or pioglitazone is
not appropriate.[55] [131] [132]

American Diabetes Association (ADA)/European
Association for the Study of Diabetes (EASD)
» The recommendations in this topic are

based primarily on NICE guidelines, which
are glucocentric in their approach, with
SGLT2 inhibitors and glucagon-like peptide
1 (GLP-1) receptor agonists generally only
recommended as second-line options for
people with elevated glucose levels after
metformin treatment.[55] However, since
the publication of the NICE guideline, some
treatment strategies have shifted to a focus on
the absolute reduction of cardiovascular and
kidney disease outcomes instead of being led
MANAGEMENT
by glycaemic control. In practice, therefore,

monotherapy with an SGLT2 inhibitor or a GLP-1
receptor agonist is increasingly used as a first-
line alternative to metformin.[130] This is based
on evidence from high-quality randomised trials
demonstrating atherosclerotic cardiovascular
Acute
disease (CVD) and chronic kidney disease
benefits independent of medications’ glucose-
lowering potential.[129] In particular, SGLT2
inhibitors appear to have benefits in patients
with type 2 diabetes who have more than
three risk factors for CVD, and both SGLT2
inhibitors and GLP-1 receptor agonists appear
beneficial in those with established CVD and/or
renal disease.[125] [128] [130] [BMJ: SGLT-2
inhibitors or GLP-1 receptor agonists for adults
with type 2 diabetes] (https://www.bmj.com/
content/373/bmj.n1091)
» A 2019 update to a joint consensus report

from the ADA and EASD recommends that if
a patient with type 2 diabetes has established
CVD, there is a compelling indication for
SGLT2 inhibitor.[129] The ADA and EASD
also recommend, if a patient with type 2
diabetes is at high risk of CVD, considering
SGLT2 inhibitor independently of their baseline
HbA1c or individualised HbA1c target with the
aim of reducing major cardiovascular events
or death and slowing progression of kidney
impairment.[129]
» NICE updated its guideline in November

2021 to recognise a separate role for SGLT2
inhibitors - regardless of glycaemic control -
for some patients with CKD. In practice, if the
patient has CKD with eGFR >45 mL/minute/1.73
m², it may be appropriate for them to take an
SGLT2 inhibitor for both antihyperglycaemic and
renal benefit (see Add-on pharmacotherapy for
patients with CKD in the Initial timeframe for
advice on when to use an SGLT2 inhibitor in
people with CKD). However, if the patient has
CKD with eGFR <45 mL/minute/1.73 m², the
glucose-lowering effects of SGLT2 inhibitors will
be negligible and therefore they will need an
alternative antihyperglycaemic agent for initial
glucose-lowering therapy.
CKD
MANAGEMENT

79
Acute


HbA1c above goal on 1st dual therapy
monotherapy
Primary options
DPP-4 inhibitor plus a thia zolidinedione
-or-
-or-
-or-
--AND--
maximum 45 mg/day
OR
MANAGEMENT
DPP-4 inhibitor plus a sulfonylurea

-or-
Acute
-or-
-or-
--AND--
-or-
4-6 mg/day
OR
Thia zolidinedione plus a sulfonylurea

maximum 45 mg/day
--AND--
-or-
4-6 mg/day
» If metformin is contraindicated or not tolerated

and initial drug treatment has not continued to
control HbA1c to below the patient’s individually
agreed threshold for intensification, the
UK National Institute for Health and Care
Excellence (NICE) recommends to consider
dual therapy.[55] Suitable options are: a
dipeptidyl peptidase-4 (DPP-4) inhibitor and
pioglitazone (a thiazolidinedione); a DPP-4
inhibitor and a sulfonylurea; pioglitazone and a
sulfonylurea.[55]
MANAGEMENT
» NICE is in the process of updating

its recommendations on choice of first
intensification medication after its evidence
review highlighted the importance of
comorbidities including cardiovascular disease,
heart failure, and chronic kidney disease
81
Acute
in informing the most beneficial choice of
medication for the patient. In particular, there
is growing evidence to demonstrate the
cardiovascular and renal benefits of sodium-
glucose co-transporter-2 (SGLT2) inhibitors
and glucagon-like peptide-1 (GLP-1) receptor
agonists, over and above their glucose-lowering
effects.[138]
» Bear in mind that drugs in dual therapy should

be introduced in a stepwise manner, checking for

CKD

MANAGEMENT

Acute

2nd insulin
Primary options
OR
» insulin detemir
OR
» insulin glargine
OR

-or-
» insulin detemir
-or-
» insulin glargine
--AND--
» insulin lispro
-or-
» insulin aspart
-or-
» insulin glulisine
» If metformin is contraindicated or not tolerated,

and if dual therapy with two oral drugs (i.e.,
a dipeptidyl peptidase-4 [DPP-4] inhibitor
and pioglitazone; a DPP-4 inhibitor and a
sulfonylurea; pioglitazone and a sulfonylurea)
has not continued to control HbA1c to below
the patient’s individually agreed threshold
for intensification, the UK National Institute
for Health and Care Excellence (NICE)
recommends considering insulin-based
treatment.[55]
» When starting insulin therapy, review the

continued need for, and safety of, other blood
MANAGEMENT
glucose-lowering therapies.[55] Give careful

consideration to the drug combinations, ensuring
that they are safe and appropriate for your
patient. If possible avoid combining insulin with
pioglitazone. The UK Medicines and Healthcare
products Regulatory Agency warns that patients
83
Acute
should be observed for signs and symptoms
of heart failure, weight gain, and oedema if
pioglitazone is used in combination with insulin.
This is owing to the increased incidence of
cardiac failure when pioglitazone is used in
combination with insulin, especially in patients
with predisposing factors.[139]
» NICE recommends choosing the most

appropriate insulin type and individualised
regimen based on individual patient
circumstances.[55] Give basal isophane (NPH)
insulin injected once or twice daily according to
need.[55] Consider starting both NPH and short-
acting insulin (particularly if the person's HbA1c
is 75 mmol/mol [9.0%] or higher), administered
either separately or as a pre-mixed (biphasic)
human insulin preparation.[55] Consider
using insulin detemir or insulin glargine as
an alternative to NPH insulin if: the patient
needs assistance from a carer or healthcare
professional to inject insulin, and use of insulin
detemir or insulin glargine would reduce the
frequency of injections from twice to once
daily; or the patient’s lifestyle is restricted by
recurrent symptomatic hypoglycaemic episodes;
or they would otherwise need twice-daily NPH
insulin injections in combination with oral
glucose-lowering drugs.[55] Consider pre-
mixed (biphasic) preparations that include short-
acting insulin analogues, rather than pre-mixed
(biphasic) preparations that include short-acting
human insulin preparations, if: the patient prefers
injecting insulin immediately before a meal; or
hypoglycaemia is a problem; or blood glucose
levels rise markedly after meals.[55]
» Consider switching to insulin detemir or insulin

glargine from NPH insulin if the patient does not
reach their target HbA1c because of significant
hypoglycaemia or experiences significant
hypoglycaemia on NPH insulin irrespective
of the level of HbA1c reached.[55] Also
consider switching if the patient cannot use
the device needed to inject NPH insulin but
could administer their own insulin safely and
accurately if switched to one of the long-acting
insulin analogues or needs help from a carer
or healthcare professional to administer insulin
injections and for whom switching to one of the
long-acting insulin analogues would reduce the
MANAGEMENT
number of daily injections.
» If the patient is on a basal insulin regimen

(NPH insulin, insulin detemir, or insulin glargine),
monitor for the need for short-acting insulin
Acute
before meals (or a pre-mixed [biphasic] insulin
preparation).[55]
» If the patient is on pre-mixed (biphasic) insulin,

monitor for the need for a further injection of
short-acting insulin before meals or for a change
to a basal bolus regimen with NPH insulin
or insulin detemir or insulin glargine, if blood
glucose control remains inadequate.[55]
» Most people with type 2 diabetes will use

insulin delivery devices (insulin pens). These can
be adjusted to administer set doses of insulin,
are widely available, and offer convenience
and accuracy in insulin dosing. Less frequently,
insulin pumps and patch pump systems are
used on a case-by-case basis in people who
need multiple daily dose insulin. Insulin pumps
are typically reserved for people with type 1
diabetes. If an insulin pump is appropriate for
the patient, its use will require significant patient
engagement to achieve clinical benefits beyond
multiple daily dose injection-based therapy.
» Exogenous insulin is a very effective way to

lower serum glucose and lower HbA1c, but its
use must be guided in most patients by regular
self-monitored blood glucose testing (finger stick
blood glucose testing) or continuous glucose
monitoring.
» Hypoglycaemia (glucose ≤3.9 mmol/L

[≤70 mg/dL]) is the most serious potential
complication of insulin therapy. People who
drive need to be particularly careful to avoid
hypoglycaemia and should be warned of the
dangers. See Complications. Another significant
side effect is weight gain. Less common side
effects may include hunger, nausea, diaphoresis,
injection site irritation, or anaphylaxis.
» When basal-bolus insulin is used by motivated

and knowledgeable patients, the dose of rapid-
acting insulin that is administered before each
meal can be based on anticipated carbohydrate
content of the upcoming meal and sometimes
adjusted for anticipated physical activity.
» A correction (or adjustment) dose may be

added to the bolus insulin based on the pre-meal
blood glucose level. In practice, a conservative
approach to calculating a correction dose is to
MANAGEMENT
assume 1 unit of insulin will lower the patient’s

blood glucose by 2 to 4 mmol/L (36-72 mg/
dL). Correction dosing can also be calculated
using the patient's total daily dose of insulin
if food intake is stable. The correction dose
can be added to the patient's mealtime insulin
85
Acute
requirement (whether based on general meal
size or carbohydrate counting) and given as the
total bolus dose.
» Various pre-mixed (biphasic) insulin

formulations are available; consult your local
drug formulary for options.
Primary options
SGLT2 inhibitor
maximum 300 mg/day
OR
SGLT2 inhibitor
OR
SGLT2 inhibitor
maximum 25 mg/day
OR
SGLT2 inhibitor
15 mg/day
OR

mg/week
OR

MANAGEMENT

weekly
Acute
OR

OR

micrograms/day
OR

14 mg/day
» The UK National Institute for Health and Care

Excellence (NICE) recommends considering
a sodium-glucose co-transporter-2 (SGLT2)
inhibitor or glucagon-like peptide-1 (GLP-1)
receptor agonist in combination with insulin, with
or without other antidiabetic drugs.[55]

MANAGEMENT

87
Acute
» Only offer a GLP-1 receptor agonist in

combination with insulin with specialist care
advice and ongoing support from a consultant-
led multidisciplinary team.[55] The MHRA warns
of cases of diabetic ketoacidosis in patients
with type 2 diabetes on a combination of a
GLP-1 receptor agonist and insulin who had
doses of concomitant insulin rapidly reduced or
discontinued.[140]
» Lower doses of insulin may be required when

these drugs are added on to insulin in order to
reduce the risk of hypoglycaemia. Consult your
CKD

MANAGEMENT

Acute

» Guidelines from the National Institute

for Health and Care Excellence in the UK
recommend offering an expedited assessment
for bariatric surgery to anyone with a body mass
index (BMI) of 35 or over who has recent-onset
type 2 diabetes (diagnosis within last 10 years)
as long as they are also receiving or will receive
assessment by a clinician-led community-
based multidisciplinary team (a ‘tier 3’ service
in the UK).[98] Consider an assessment for
bariatric surgery for anyone with a BMI of 30
to 34.9 kg/m² who has recent-onset type 2
diabetes as long as they are also receiving or
will receive assessment in a ‘tier 3’ service (or
equivalent).[98] Consider an assessment for
bariatric surgery for anyone of Asian family origin
who has recent-onset type 2 diabetes at a lower
BMI than other populations as long as they are
also receiving or will receive assessment in a
‘tier 3’ service (or equivalent).[98] People of
Asian family origin have comorbidity risk factors
that are of concern at lower BMIs.
» The 2018 American Diabetes Association/

consensus guideline recommends bariatric
surgery as an option for patients with type 2
diabetes who have: a BMI ≥ 40.0 kg/m² if of non-
Asian ancestry; a BMI ≥ 37.5 kg/m² if of Asian
ancestry; a BMI of 35.0 to 39.9 kg/m² (32.5 to
37.4 kg/m² if of Asian ancestry) and who cannot
achieve durable weight loss with non-surgical
methods.[120]
MANAGEMENT
» Randomised clinical trials have shown a

benefit from bariatric surgery (also referred to
as metabolic surgery) compared with medical
therapy alone with regard to diabetes remission,
glycaemic control, need for glucose-lowering
medications, quality of life, and reduction in
89
Acute
cardiovascular risk factor markers over the
short term (e.g., 1-3 years) in people with type
2 diabetes, as well as for possible prevention
of type 2 diabetes.[184] [185] [186] [187]
[188] [189] Cohort studies suggest that both
Roux en Y bypass and sleeve gastrectomy
procedures lead to diabetes remission that
lasts a mean of about 5 years in more than half
of patients, and significantly reduce mortality,
stroke, myocardial infarction, and microvascular
complications in those with type 2 diabetes.[190]
[191] [192] Compared with sleeve gastrectomy,
Roux en Y leads to somewhat greater weight
loss and other benefits, but is a more technically
challenging operation with higher re-operation
and readmission rates. The benefits and risks
of bariatric surgery also vary substantially
across type 2 diabetes patient subgroups.
In observational studies, average benefits
appear to be highest in people with more
recent onset of type 2 diabetes, and those not
on insulin therapy.[172] [193] Benefits have
been documented in younger people (age
40-50 years) as well as those over 65 years of
age.[172] [193]
pregnant
1st low-dose aspirin

Primary options
» aspirin: 75-150 mg orally once daily
» Advise pregnant women with type 2 diabetes

to take low-dose aspirin from 12 weeks until the
birth of the baby.[16] [195] These women are at
high-risk of pre-eclampsia.[195]
adjunct met formin
Primary options

MANAGEMENT

Acute
» Women with diabetes may be advised to
use metformin with or without insulin during
pregnancy (and in the preconception period),
when the likely benefits from improved blood
glucose control outweigh the potential for
harm.[16]
» Stop all other oral blood glucose-

lowering agents before and throughout
pregnancy.[16] Women who are breastfeeding
can resume or continue metformin immediately
after birth, but should avoid other oral
blood glucose-lowering therapy while
breastfeeding.[16]
adjunct insulin
Primary options

-or-
» insulin detemir
-or-
» insulin glargine
--AND--
» insulin lispro
-or-
» insulin aspart

Excellence in the UK recommends isophane
(NPH) insulin as the first choice for long-
acting insulin during pregnancy.[16] Consider
continuing treatment with long-acting insulin
analogues (insulin detemir or insulin glargine) for
women with diabetes who have established good
blood glucose control while using these before
pregnancy.[16]
» The available evidence on rapid-acting insulin

analogues (insulin aspart and insulin lispro) does
not show an adverse effect on pregnancy or the
health of the baby.[16]
» Advise pregnant women with diabetes who

are on insulin to maintain their capillary plasma
glucose level above 4 mmol/L (72 mg/dL).[16]
» In practice, the majority of pregnant women

with type 2 diabetes will need insulin.
MANAGEMENT
plus lifestyle measures and review medication

91
Acute
» As well as lifestyle advice for non-pregnant
people with type 2 diabetes (see the Initial
timeframe), give specific advice to patients who
are planning pregnancy or are pregnant.
» Women with type 2 diabetes should use an

effective method of contraception until they plan
pregnancy.[16] Women should be evaluated
before pregnancy for retinopathy, nephropathy,
neuropathy, and possible cardiovascular
disease, which may worsen during or complicate
pregnancy.[16]
» Explain to women with diabetes who are

planning pregnancy that if they have good
blood glucose control before conception and
throughout their pregnancy, this will reduce the
risk of miscarriage, congenital malformation,
stillbirth, and neonatal death. Also explain that
the risks can be reduced but not eliminated.[16]
» Agree individualised targets for self-monitoring

of blood glucose with women who have diabetes
and are planning a pregnancy, taking into
account the risk of hypoglycaemia.[16]

that HbA1c should be <48 mmol/mol (6.5%)
before conception if this can be achieved without
problematic hypoglycaemia.[16] Any reduction
towards this target is likely to reduce the risk of
congenital malformations. NICE recommends
up to monthly measurement of HbA1c levels
for women with diabetes who are planning a
pregnancy.[16] Strongly advise women with
diabetes whose HbA1c level is above 86
mmol/mol (10%) not to get pregnant until their
HbA1c level is lower, because of the associated
risks.[16]
» Review the patient’s medication. Stop any

drugs contraindicated in pregnancy if your
patient is planning pregnancy or as soon as
pregnancy is confirmed; use alternative agents
that are suitable for pregnant women. Stop ACE
inhibitors and angiotensin-II receptor antagonists
before conception, or as soon as pregnancy
is confirmed.[16]Stop SGLT2 inhibitors if the
patient is planning pregnancy, or as soon as
pregnancy is confirmed.[133] Stop statins
before pregnancy, or as soon as pregnancy
MANAGEMENT
is confirmed.[16] Women with diabetes who

are breastfeeding should continue to avoid any
medicines for their diabetes complications that
were stopped for safety reasons when they
started planning the pregnancy.[16]
Acute
» Advise women who are planning a pregnancy
to take folic acid, which should be continued until
12 weeks of gestation.[16] Women with diabetes
have an increased risk of having infants with
neural tube defects, compared with the general
population.[194]

» During pregnancy, women should be cared for

by a multidisciplinary team, including a dietitian,
a nurse educator, an endocrinologist, and an
obstetrician.
» Offer pregnant women with pre-existing

diabetes retinal assessment by digital imaging
with mydriasis using tropicamide following their
first antenatal clinic appointment (unless they
have had a retinal assessment in the last 3
months), and again at 28 weeks. If any diabetic
retinopathy is present at booking, perform
an additional retinal assessment at 16 to 20
weeks.[16]
» NICE guidelines recommend the following

blood glucose targets in pregnant women with
pre-existing type 2 diabetes (as long as these
are achievable without causing problematic
hypoglycaemia): fasting: <5.3 mmol/L (<95.4 mg/
dL); 1 hour after meals: <7.8 mmol/L (<140.4
mg/dL); 2 hours after meals: <6.4 mmol/L
(<115.2 mg/dL).[16] [Evidence C]
» Measure HbA1c levels in all pregnant women

with pre-existing diabetes at the booking
appointment to determine the level of risk for the
pregnancy. Consider measuring HbA1c levels
in the second and third trimesters of pregnancy
MANAGEMENT
for women with pre-existing diabetes to assess

the level of risk for the pregnancy.[16] Good
glucose control with HbA1c as close to normal
as is safely possible (ideally HbA1c <48 mmol/
mol [<6.5%]) before conception and during
93
Acute
pregnancy optimises maternal and fetal health
outcomes.[16]
» Pregnant women should test their fasting,

pre-meal, 1-hour post-meal, and bedtime
blood glucose levels every day.[16] The pattern
should be examined every few weeks early
in pregnancy so that nutrition content and
timing, exercise patterns, and the insulin doses
can be modified to achieve optimal control.
Insulin requirements generally increase early in
pregnancy, then decrease from about 8 to 16
weeks before rising throughout the rest of the
pregnancy.
Primary prevention
Lifestyle factors (e.g., obesity and stress) seem to be the main drivers of the current type 2 diabetes
epidemic. Particular conditions can increase the risk of type 2 diabetes. These include: cardiovascular
disease, hypertension, obesity, stroke, polycystic ovary syndrome, a history of gestational diabetes, and
mental health problems.[11] With aggressive prevention of obesity in all age groups, type 2 diabetes is
potentially preventable.[24] [25]
In the UK, the NHS Diabetes Prevention Programme (DPP) identifies people with modifiable risk factors and
non-diabetic hyperglycaemia (NDH), defined as HbA1c 42 to 47 mmol/mol (6.0% to 6.4%) or fasting plasma
glucose 5.5 to 6.9 mmol/L (99.0 to 124.2 mg/dL). Participants can self-refer or they might be identified by
another means (e.g., their medical records). The DPP offers tailored, personalised help, including education
on lifestyle choices, advice on how to reduce weight through healthier eating, and bespoke physical activity
programmes.[26]
The National Institute for Health and Care Excellence (NICE) in the UK recommends a two-stage strategy
to identify people at high risk of type 2 diabetes (and those with undiagnosed type 2 diabetes): a risk
assessment and, if necessary, a confirmatory blood test.[11] NICE recommends that general practitioners
(primary care physicians) use a validated computer-based risk-assessment tool to identify people on their
practice register who may be at high risk of type 2 diabetes.[11] Risk assessment should be offered to:[11]
• All adults aged 40 and above (except pregnant women)

• People aged 25 to 39 of South Asian, Chinese, African-Caribbean, and black African ethnicity (except
pregnant women)
• Adults with any other condition that increases the risk of type 2 diabetes.
Those with a high risk score should be offered a fasting plasma glucose or HbA1c test.[11] People identified
as being at high risk of progression to type 2 diabetes (fasting plasma glucose of 5.5 to 6.9 mmol/L [99.0 to
124.2 mg/dL] or HbA1c of 42 to 47 mmol/mol [6.0% to 6.4%]) should be offered a referral to an evidence-
based, quality-assured intensive lifestyle-change programme.[11]
Several clinical trials have shown that weight loss is associated with delayed or decreased onset of type 2
diabetes in high-risk adults.[13] [27] [28] [29] [30] [31] Progression to diabetes from NDH can be reduced
by 50% over 3 to 4 years through modest weight loss (7% of body weight) using diet and regular physical
activity.[27] In addition, several pharmacological agents, including metformin, alpha-glucosidase inhibitors,
MANAGEMENT
orlistat, glucagon-like peptide 1 (GLP-1) receptor agonists, and thiazolidinediones, have been shown to
reduce progression from NDH to type 2 diabetes.[15] [32] [33] [34] [35] Lifestyle change and/or metformin
are preferred for most patients.[36] [37] [38] [39] More aggressive multi-agent pharmacological approaches
remain controversial.[40] Screening for NDH and cardiovascular risk reduction appropriate to the needs of
the individual are also very important.[41] [42] [43]
Secondary prevention
The risk of macrovascular complications can be reduced by over 50% using effective multifactorial
interventions.[228]
Other preventative measures currently recommended for people with type 2 diabetes in the UK include:
• Annual influenza immunisations for those who require insulin or oral hypoglycaemic drugs[229]
• Vaccination against pneumococcal disease for those with diabetes requiring insulin or antidiabetic
medication[230]
• Regular dental care
• Structured, tailored diabetes education, with annual reinforcement and review.[231]
Patient discussions
Advise the patient that frequent medication adjustments represent good care, and are not a sign of failure
or a reason for self-blame or guilt.
• The use of self-monitoring of blood glucose data to promptly identify loss of glucose control and
proactively adjust therapy is an essential self-management skill when using multi-dose insulin
regimens, and requires patient education and easy access to health team members between
scheduled surgery visits. Those on multi-dose insulin regimens are often advised to monitor blood
sugars before meals and at bedtime.
• In other patients with diabetes, self-monitoring may be useful to assess the impact of changes in
diet, medication regimen, and exercise, as well as to guide dietary and fluid intake and medication
management during episodes of illness.[225] [227]
Counsel women of childbearing age with diabetes about the importance of strict glycaemic control prior to
conception.[16]
Arrange for the patient to have counselling on how to prevent and promptly identify eye, foot, kidney, and
cardiovascular complications.
Explain to the patient that low blood sugar (glucose ≤3.9 mmol/L [≤70 mg/dL]) is often accompanied by
symptoms such as tachycardia, sweating, shakiness, intense hunger, or confusion, and must be dealt with
promptly by ingesting 15-20 g of carbohydrate (equivalent to 3 to 4 glucose tablets of 5 grams per tablet).
• People who drive need to be particularly careful to avoid hypoglycaemia and should be warned of
the dangers.
• After self-treatment, blood sugar should be checked if possible.
• Instruct patients to promptly report nocturnal hypoglycaemia or recurrent episodes of
hypoglycaemia so that therapy may be adjusted.
• Patients should have a carbohydrate snack prior to exercise if self-monitored blood glucose is <5.6
mmol/L (<100 mg/dL) and the patient is taking insulin or an insulin secretagogue (sulfonylurea or
meglitinide). Patients using alpha-glucosidase inhibitors who experience hypoglycaemia must use
glucose tablets because absorption of conventional carbohydrates is slowed by the treatment.
• Those at risk of clinically significant hypoglycaemia (glucose <3.0 mmol/L [<54 mg/dL]) should
MANAGEMENT
have injectable glucagon available, and a close companion should be instructed on how to inject
glucagon.[15]
Ensure the patient is aware that any intercurrent illness can cause glucose levels to rise.[182] Give the
patient clear and individualised oral and written advice (‘sick-day rules’) about how to adapt management
during intercurrent illness. Some drugs need to be suspended during intercurrent illness; it is important to
ensure the patient is aware that they will need to restart any suspended medication once they are feeling
95
better and able to eat and drink. [DiabetesontheNet: sick day rules] (https://diabetesonthenet.com/wp-
content/uploads/pdf/dotn024ae8fb1b78500b7bc752b98e9b6d92.pdf)
MANAGEMENT
Type 2 diabetes in adults Follow up
Monitoring
Monitoring
FOLLOW UP
Optimal diabetes care requires a long-term relationship with the patient; appropriate use of consultants
when needed; regular monitoring and control of blood pressure, HbA1c, and tobacco use; and supported
lifestyle changes.
On diagnosis:
• Immediately refer the patient to the local eye screening service[55]

• Assess the patient’s risk of developing a diabetic foot problem; also do this at least annually
thereafter and whenever any foot problems arise[56]
• Measure the patient’s urine albumin to creatinine ratio and continue to check this every year.
Measure HbA1c levels at diagnosis and:[55]
• Every 3 to 6 months (tailored to individual needs), until the patient’s HbA1c is stable on unchanging
therapy
• Every 6 months once the patient’s HbA1c level and blood glucose-lowering therapy are stable.
Most patients require diabetes assessments every 3 to 6 months, and some patients may benefit from
more frequent visits, especially when motivated to improve their care.
Measure blood pressure at least once a year in an adult with type 2 diabetes without previously
diagnosed hypertension or renal disease.[57]
• Offer and reinforce preventive lifestyle advice.[57]

Ensure the patient receives ongoing individualised nutritional advice from a healthcare professional with
specific expertise and competencies in nutrition.[55]
Aim to make a routine assessment of frailty whenever you review an older person with diabetes.[58] [59]
[60] Use a validated tool (e.g., the electronic Frailty Index (eFI), the Rockwood frailty score, or Timed
Up and Go) to confirm clinical suspicion of frailty.[59] [60] Frail patients need a tailored approach to
management; consult a specialist if you need guidance.
Use of diabetes educators is recommended, although traditional information-based diabetes patient

education mandated by some professional organisations is only moderately effective in randomised
studies.[223] [224] A multidisciplinary team with access to nurses, educators, dietitians, clinical
pharmacologists, psychologists, and other specialists as needed is recommended. Patient readiness
to change is a strong predictor of improved care, and readiness to change may vary across the clinical
domains of blood pressure, statin use, aspirin use, glucose, smoking, physical activity, and nutrition.
Rapid assessment of readiness to change, and directing care to the domain with maximum potential to
change, is advised.[95]
Self-management by regular blood glucose monitoring is not routinely recommended in patients with
type 2 diabetes, because it does not significantly improve glycaemic control, health-related quality
of life, or hypoglycaemia rates.[55] [225] [Evidence C] However, self-monitoring of blood glucose is
recommended for those who (a) are on insulin; (b) have had prior hypoglycaemic episodes; (c) drive
or operate machinery and use oral medications that increase their risk of hypoglycaemia; or (d) are
pregnant, or planning to become pregnant.[55]
In addition to care required to achieve recommended levels of blood pressure and glucose control, as well
as lifestyle changes including not smoking, the following periodic monitoring for complications is advised:
• Eye screening every year[226]
97
• Annual assessment of renal function including both a urinary albumin excretion test and a serum
creatinine test with estimated glomerular filtration rate (eGFR) based on the CKD-EPI creatinine
equation or equivalent
• Annually or more frequent foot examinations[56]
FOLLOW UP
• Including assessment of ankle reflexes, dorsalis pedis pulse, vibratory sensation, and 10-
gram monofilament touch sensation
• All patients with insensate feet, foot deformities, or a history of foot ulcers or amputation
should have their feet examined at every visit and are candidates for specialised
footwear.[15]
Due to disease progression, comorbidities, and non-adherence to lifestyle or medication, a substantial

fraction of patients who achieve recommended goals for HbA1c, blood pressure, and lipid management
relapse to uncontrolled states of one or more of these within 1 year. Relapse is usually asymptomatic;
frequent monitoring of clinical parameters is desirable to anticipate or detect relapse early and adjust
therapy.
Factors that may lead to loss of adequate glycaemic control include medication non-adherence,
depression, musculoskeletal injury or worsening arthritis, competing illnesses perceived by the patient
as more serious than diabetes, social stress at home or at work, substance abuse, occult infections, use
of medications (such as corticosteroids, certain depression medications [paroxetine], mood stabilisers,
or atypical antipsychotics) that elevate weight or glucose, or other endocrinopathies such as Cushing's
disease.
Loss of control of blood pressure and lipids is also a common phenomenon. Close monitoring of patients
with diabetes through frequent visits and lab work helps to maintain patients at treatment goals and
proactively identify upward trends in blood pressure or HbA1c, and to reinforce the importance of statin
adherence (if indicated) and non-smoking.
Complications
Complications Timeframe Likelihood
FOLLOW UP
diabetic kidney disease long term low
Chronic kidney disease occurs in about 40% of patients with type 2 diabetes over time. Prevalence
of end-stage renal disease is about 1% in those with type 2 diabetes (cross-sectional data).[200]
Chronic kidney disease is driven by uncontrolled blood pressure and glucose, and increases the risk
of cardiovascular disease at least fourfold. An estimated glomerular filtration rate (eGFR) <60 mL/
minute/1.73 m² establishes a diagnosis of chronic kidney disease, and microalbuminuria or albuminuria
establishes a diagnosis of nephropathy. Either of these findings should prompt increased efforts to
aggressively manage systolic blood pressure, avoid non-steroidal anti-inflammatory drugs, and consider
use of antihyperglycaemic drugs with low risk of hypoglycaemia and pronounced renal benefits (especially
sodium-glucose co-transporter-2 [SGLT2] inhibitors or glucagon-like peptide-1 [GLP-1] agonists).[210]
[211]
Also important are use of an ACE inhibitor or angiotensin-II receptor antagonist, and optimisation of
glucose control. When eGFR is lower than 30 mL/minute/1.73m², referral to a nephrologist for expectant
management of end-stage renal disease is necessary.
Renal failure predisposes patients to anaemia and hypoglycaemia; in renal failure, insulin doses may need
to be reduced.
impaired vision long term low
In a global study, prevalence of diabetic retinopathy in newly diagnosed type 2 diabetes varied from 1.5%
to 31%, with higher prevalence observed in developing countries.[212] Risk of vision loss is increased
by poor blood pressure and glucose control, and by failure to regularly screen for retinopathy, macular
degeneration, glaucoma, and cataracts.[213] [214] The risk of all of these eye conditions is increased in
diabetes.
lower extremity amputation long term low
Incidence of lower extremity amputation (LEA) is between 2.5 and 4 per 1000 people with diabetes per
year, with significant geographic variation in LEA rates within countries.[215] Incidence rates of major LEA,
defined as loss of lower limb through or above the ankle, are declining in patients with diabetes; however,
there is some evidence that minor LEA (loss of lower limb below the level of the ankle) incidence rates are
increasing, with about half being toe or metatarsal amputations.[197]
Risk is aggravated by neuropathy and by peripheral vascular disease, and can be reduced by smoking
cessation; aggressive management of glucose, blood pressure, and lipids; use of customised footwear
in patients with known neuropathy or foot deformity; and prompt and aggressive management of lower
extremity infections.
cardiovascular disease variable high
Cardiovascular disease (CVD) and CVD-associated mortality is declining in patients with diabetes,
particularly in high-income countries.[197] Adults with type 2 diabetes are twice as likely to die of stroke
or myocardial infarction compared with those without diabetes, and they are more than 40 times more
likely to die of macrovascular than to die of microvascular complications of diabetes.[87] [88] To reduce
cardiovascular risk, blood pressure, lipids, and tobacco use should be adequately managed. Use of
statins, ACE inhibitors, metformin, aspirin, empagliflozin, liraglutide, and proprotein convertase subtilisin/
kexin type 9 (PCSK9) inhibitors may reduce cardiovascular mortality or all-cause mortality in selected
patients with type 2 diabetes. In the ACCORD and ADVANCE randomized trials, near-normal glucose
99

control failed to decrease cardiovascular mortality or all-cause mortality in type 2 diabetes, and in one
of those studies, increased all-cause mortality. However, ACCORD and ADVANCE trials did not use
FOLLOW UP
empagliflozin, liraglutide, or PCSK9 inhibitors. Many studies suggest that HbA1c ≥64 mmol/mol (≥8%)
increases risk of major cardiovascular events.[124] [125]
Increased fatigability may be an early warning sign of progressive cardiovascular disease; clinicians
should have a low threshold for cardiac evaluation of any symptoms that are potentially cardiac-related in
patients with type 2 diabetes.
congestive heart failure (CHF) variable high
Diabetes is a risk factor for CHF, with poor glycaemic control associated with greater risk for the
development of CHF and worsening of clinical outcomes for patients with CHF and diabetes.[202] CHF
occurs in up to 10% to 15% of patients with diabetes.[203] CHF in type 2 diabetes is often related to
uncontrolled hypertension, or ischaemic coronary disease, but may also occur as a microvascular
complication of diabetes.
Requires management with ACE inhibitor/angiotensin-II receptor antagonist, diuretics, and other
medications.
Must rule out underlying causes such as myocardial infarction, atrial fibrillation, thyroid disorders, anaemia,
or structural heart disease.
stroke variable high
Related to uncontrolled blood pressure, glucose, and lipids. Lifetime risk is higher in women than in men
with diabetes.[204]
Prompt hospitalisation and neurological evaluation, with possible emergency use of tissue plasminogen
activator or other therapeutic strategies, may minimise damage and maximise potential for recovery of
function.
infection variable medium
Hyperglycaemia compromises defence against bacterial infections by several mechanisms including

impaired phagocytosis.
Normalisation of blood glucose reduces the risk of infections, especially cystitis, cellulitis, and pneumonia.
Immunisation reduces the risk of serious pneumococcal, Haemophilus influenzae , and influenza
infections.
Aggressive infection-specific therapy and supportive therapy including adequate glucose control are key to
successful treatment.
periodontal disease variable medium
Type 2 diabetes is associated with periodontal disease, but causality is not established.[205] In one large
epidemiological survey, periodontal disease was an independent predictor of incident diabetes.[205]
Bidirectional risk has been postulated.[206]
Control of periodontal disease and hyperglycaemia are mutually beneficial. Routine preventative dental
care is important for people with type 2 diabetes.[205]

treatment-related hypoglycaemia variable medium
FOLLOW UP
Hypoglycaemia is the most common and potentially most serious side effect of insulin and/or insulin
secretagogues (sulfonylureas or meglitinides), alone or in combination with other drugs. It can lead
to decreased quality of life; severe hypoglycaemia is a medical emergency that can cause confusion,
seizures, and coma. Severe hypoglycaemia is defined as any low blood glucose level leading to cognitive
impairment requiring assistance from another person for recovery. A glucose alert value is defined as
≤3.9 mmol/L (≤70 mg/dL), requiring treatment with fast-acting carbohydrate and dose adjustment of
glucose-lowering therapy. Serious clinically significant hypoglycaemia is defined as <3.0 mmol/L (<54
mg/dL).[15] Low blood sugars are common in patients who are trying to achieve HbA1c <53 mmol/mol
(<7%). Hypoglycaemia is usually associated with warning signs, such as rapid heartbeat, perspiration,
shakiness, anxiety, confusion, and hunger. Hypoglycaemia unawareness (absence of symptoms during
hypoglycaemia) and severe hypoglycaemia, defined as a blood sugar so low that assistance from another
person or medical personnel is required to treat it, occurs in 1% to 3% of type 2 diabetes patients per year.
Older people and those with comorbid heart disease, congestive heart failure, chronic kidney disease, or
depression are at substantially increased risk for severe hypoglycaemia.[207]
Patients should be counselled on recognition, prevention, and treatment of hypoglycaemia and should
carry with them glucose tablets or comparable fast-acting carbohydrate product. People who drive need to
be particularly careful to avoid hypoglycaemia and should be warned of the dangers. Patients using alpha-
glucosidase inhibitors must use glucose tablets for hypoglycaemia because absorption of conventional
carbohydrates is slowed by the medication.
depression variable medium
When glycaemic goals or adherence to treatment plan are difficult to achieve, the presence of depression
should be considered. Screening with a validated tool such as the Patient Health Questionnaire (PHQ)-9
may help with identification and diagnosis. The cross-sectional prevalence of depression is 10% to
25% in people with diabetes.[218] Adults with type 2 diabetes diagnosed before age 40 years have
excess hospitalisations across their lifespan, which includes a large burden of mental illness in young
adulthood.[219]
obstructive sleep apnoea variable medium
Obstructive sleep apnoea is common among overweight and obese adults, and has been associated with
insulin resistance and altered glucose metabolism. Further studies are needed to assess the effect of
continuous positive airway pressure on glycaemic control, as results have varied.[220] [221] [222]
The American Diabetes Association recommends assessment of sleep pattern and duration as part of a
comprehensive approach to lifestyle and glycaemic control.[15]
diabetic ketoacidosis (DKA) variable low
Commonly thought of in type 1 diabetes; however, can occur in type 2 diabetes and an unusual type of
diabetes known as ketosis-prone diabetes. Infection and poor diabetic medication adherence are the most
common reasons for developing DKA, but no precipitating factors may be apparent.[208]
Criteria of DKA is the same, regardless of type of diabetes and is potentially fatal if not properly treated.
Hydration, parenteral insulin therapy, intensive monitoring, and careful management of electrolyte
imbalances and acidosis are important for successful therapy.
101

non-ketotic hyperosmolar state variable low
FOLLOW UP
Occurs most commonly in older people with type 2 diabetes and usually evolves insidiously over days
to weeks.[209] Characterised by severe hyperglycaemia, hyperosmolality, and volume depletion, in the
absence of severe ketoacidosis.
Hydration, insulin therapy, and careful clinical and laboratory monitoring are the basis of successful
therapy.
autonomic or peripheral neuropathy variable low
Diabetic peripheral neuropathy is the most common chronic complication of diabetes, characterised by the
presence of peripheral nerve dysfunction, diagnosed after the exclusion of other causes.[216] Pain is the
outstanding complaint in most patients, but many patients are completely asymptomatic.
Manifestations of autonomic neuropathy may include: erectile dysfunction, diarrhoea, gastroparesis, or

orthostatic hypotension.
For type 2 diabetes the effects of glycaemic control on peripheral or autonomic neuropathy are less clear
than for type 1 diabetes, with early data suggesting that glucose control is beneficial if started earlier in the
disease course, but later studies not confirming these findings.[217]
Prognosis
Diabetes increases the likelihood of major cardiovascular events and death, but the increased risk is
variable across patients depending on age at diabetes onset, duration of diabetes, glucose control, blood
pressure control, lipid control, tobacco control, renal function, microvascular complication status, and other
factors. The association of diabetes and increased mortality can be attenuated by cardiovascular risk factor
control.[196] A HbA1c of 6% to 6.9% (42-52 mmol/mol) is associated with the lowest mortality.[196] Trends
in data for complications in people with diabetes show a declining risk of cardiovascular disease (CVD) and
CVD-associated mortality, particularly in high-income countries.[197] When type 2 diabetes is diagnosed
at age 40, men lose an average of 5.8 years of life, and women lose an average of 6.8 years of life.[6] The
overall excess mortality in those with type 2 diabetes is around 15% higher, but ranges from ≥60% higher in
younger adults with poor glucose control and impaired renal function, to better than those without diabetes
for those who are age 65 and over with good glucose control and no renal impairment.[87] [88]
Diabetic retinopathy is the most common cause of blindness in people of working age in England,
Wales, and Scotland.[198] About 12% to 19% of people with type 2 diabetes have some diabetic
retinopathy already at the time of diagnosis; 4% develop proliferative retinopathy after 20 years or more of
diabetes.[199] Prevalence of end-stage renal disease (ESRD) is about 1% in those with type 2 diabetes
(cross-sectional data), but cumulative prevalence of nephropathy and/or chronic kidney disease is much
higher.[200] Incidence rates of ESRD attributed to diabetes are declining; however, continued intervention
to detect and manage diabetic kidney disease is required to limit the development of ESRD.[201] Effective
treatment requires a motivated and informed patient who actively takes responsibility for the care of their
diabetes, and a clinical team willing to frequently adjust medications to support comprehensive disease
management over a long period of time.
Type 2 diabetes in adults Guidelines
Diagnostic guidelines
United Kingdom
Type 2 diabetes in adults: management (ht tps://www.nice.org.uk/guidance/

ng28)
Published by: National Institute for Health and Care Excellence Last published: 2022
Diabetes in pregnancy: management from preconception to the postnatal

period (ht tps://www.nice.org.uk/guidance/ng3)
Type 2 diabetes: prevention in people at high risk (ht tps://www.nice.org.uk/

guidance/ph38)
GUIDELINES
Europe
Guidelines on diabetes, pre-diabetes, and cardiovascular diseases (ht tps://

www.escardio.org/Guidelines)
Published by: European Society of Cardiology; European Association Last published: 2019
for the Study of Diabetes
International
Managing type 2 diabetes in primary care (ht tps://idf.org/e-library/

guidelines.html)
Published by: International Diabetes Foundation Last published: 2017
Managing older people with type 2 diabetes: global guidelines (ht tps://idf.org/
e-library/guidelines.html)
103
North America
Standards of medical care in diabetes - 2022 (ht tps://

professional.diabetes.org/content-page/practice-guidelines-resources)
Published by: American Diabetes Association Last published: 2022
Prediabetes and type 2 diabetes: screening (ht tps://

www.uspreventiveservicestaskforce.org/uspst f/recommendation/screening-
for-prediabetes-and-type-2-diabetes)
Published by: US Preventive Services Task Force Last published: 2021
Primary prevention of ASCVD and T2DM in patients at metabolic risk (ht tps://
www.endocrine.org/clinical-practice-guidelines/guidelines-by-year)
Published by: Endocrine Society Last published: 2019
Treatment of diabetes in older adults (ht tps://www.endocrine.org/clinical-

GUIDELINES
practice-guidelines/guidelines-by-year)
Guideline on the primary prevention of cardiovascular disease (ht tps://

professional.heart.org/en/guidelines-and-statements/guidelines-and-
statements-search)
Published by: American College of Cardiology; American Heart Last published: 2019
Association
Guideline on the management of blood cholesterol (ht tps://

statements-search)
Published by: American Heart Association; American College of Last published: 2019
Cardiology
Diabetes Canada clinical practice guidelines (ht tp://guidelines.diabetes.ca/

fullguidelines)
Published by: Diabetes Canada Last published: 2018
Guideline for the prevention, detection, evaluation, and management of high

blood pressure in adults (ht tps://professional.heart.org/en/guidelines-and-
statements/guidelines-and-statements-search)
Published by: American College of Cardiology; American Heart Last published: 2017
Association
Treatment guidelines
United Kingdom
Type 2 diabetes in adults: management (ht tps://www.nice.org.uk/guidance/

ng28)
Diabetes in pregnancy: management from preconception to the postnatal

period (ht tps://www.nice.org.uk/guidance/ng3)
Diabetic foot problems: prevention and management (ht tps://

www.nice.org.uk/guidance/ng19)
GUIDELINES
Managing frailty and associated comorbidities in older adults with diabetes
(ht tps://abcd.care/resource/managing-frailty-and-associated-comorbidities-
older-adults-diabetes-position-statement)
Published by: Association of British Clinical Diabetologists Last published: 2019
Community pharmacies: promoting health and wellbeing (ht tps://

Pharmacological management of glycaemic control in people with type 2

diabetes (ht tps://www.sign.ac.uk/our-guidelines)
Published by: Scottish Intercollegiate Guidelines Network Last published: 2017
Management of diabetes (ht tps://www.sign.ac.uk/our-guidelines)

Published by: Scottish Intercollegiate Guidelines Network Last published: 2017
Europe
Guidelines on diabetes, pre-diabetes, and cardiovascular diseases (ht tps://

www.escardio.org/Guidelines)
Published by: European Society of Cardiology Last published: 2019
105
International
2019 update to: management of hyperglycaemia in type 2 diabetes (ht tps://

www.easd.org/statements.html)
Published by: American Diabetes Association; European Association for Last published: 2019
the Study of Diabetes
Management of hyperglycemia in type 2 diabetes (ht tps://www.easd.org/

statements.html)
Published by: American Diabetes Association; European Association for Last published: 2018
the Study of Diabetes
Guidelines on second- and third-line medicines and type of insulin for the
control of blood glucose levels in non-pregnant adults with diabetes mellitus
(ht tps://apps.who.int/iris/handle/10665/272433)
Published by: World Health Organization Last published: 2018
GUIDELINES
Managing type 2 diabetes in primary care (ht tps://idf.org/e-library/guidelines)

The Diabetes Surgery Summit II guidelines: a disease-based clinical

recommendation (ht tps://www.ncbi.nlm.nih.gov/pubmed/27189354)
Published by: The Second Diabetes Surgery Summit Last published: 2016
Managing older people with type 2 diabetes: global guidelines (ht tps://idf.org/
e-library/guidelines)
North America
Standards of medical care in diabetes - 2022 (ht tps://

professional.diabetes.org/content-page/practice-guidelines-resources)
Published by: American Diabetes Association Last published: 2022
Treatment of diabetes in older adults (ht tps://www.endocrine.org/clinical-

practice-guidelines/guidelines-by-year)
Guideline on the management of blood cholesterol (ht tps://

statements-search)
Published by: American Heart Association; American College of Last published: 2019
Cardiology
GUIDELINES
Diabetes Canada clinical practice guidelines (ht tp://guidelines.diabetes.ca/
fullguidelines)
Published by: Diabetes Canada Last published: 2018
Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice

guideline update (ht tps://www.acponline.org/clinical-information/guidelines)
Published by: American College of Physicians Last published: 2017
107
Type 2 diabetes in adults Online resources
Online resources
1. QRISK calculator (https://qrisk.org/three) (external link)
2. BMJ: SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes (https://
www.bmj.com/content/373/bmj.n1091) (external link)
3. DiabetesontheNet: sick day rules (https://diabetesonthenet.com/wp-content/uploads/pdf/

dotn024ae8fb1b78500b7bc752b98e9b6d92.pdf) (external link)
ONLINE RESOURCES
Type 2 diabetes in adults Evidence tables
Evidence tables
What are the effects of tighter blood glucose control compared with less tight
EVIDENCE TABLES
blood glucose control in pregnant women with gestational diabetes?[16]
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review)
that focuses on the above important clinical question.
View the full source guideline (https://www.nice.org.uk/guidance/ng3)
Evidence C * Confidence in the evidence is very low or low where GRADE has been performed
and the intervention may be more effective/beneficial than the comparison for key
outcomes. However, this is uncertain and new evidence could change this in the
future.
Population: Pregnant women with gestational diabetes ᵃ

Intervention: Tighter glucose control
Comparison: Less tight glucose control
† ‡
Outcome Effectiveness (BMJ rating) Confidence in evidence (GRADE)
Fasting blood glucose < 5.3 mmol/L versus ≥5.3 mmol/L in women with gestational diabetes
Pre-eclampsia Favours intervention Very Low
Large for gestational age Favours intervention Very Low
Strict control of 1.5 hour postprandial blood glucose (< 6.7 mmol/L) versus customary control (<7.8 mmol/L)
in women with pre-existing type 1 diabetes ᵃ
Mean HbA1c (by trimester) ᵇ No statistically significant Very Low

difference
1 to 2 hour postprandial blood glucose of ≤7.8 mmol/L versus >7.8 mmol/L in women with pre-existing
diabetes ᵃ
Macrosomia at 29 to 32 weeks’ Favours intervention Very Low

gestation
2 hour postprandial blood glucose <6.4 mmol/L versus ≥6.4 mmol/L in women with gestational diabetes
Pre-eclampsia Favours intervention Very Low
Large for gestational age Favours intervention Very Low
Recommendations as stated in the source guideline
109
The National Institute of Health and Care Excellence (NICE) 2015 guideline on Diabetes in Pregnancy makes
the following recommendation:
EVIDENCE TABLES
Advise pregnant women with any form of diabetes to maintain their capillary plasma glucose below the
following target levels, if these are achievable without causing problematic hypoglycaemia:
• Fasting: 5.3 mmol/litre AND

• 1 hour after meals: 7.8 mmol/litre OR
• 2 hours after meals: 6.4 mmol/litre.
Note
The guideline committee noted that some of the included studies used very short gestational intervals and
that blood glucose control may require adjusting for women depending on their personal circumstances and
treatment.
ᵃ The guideline committee considered evidence for pregnant women with type 1 diabetes, type 2 diabetes,
or gestational diabetes. They extrapolated the evidence to all women with diabetes during pregnancy, as
ideally blood glucose levels during pregnancy should be as near to normal as is possible, without increasing
the risk of hypoglycaemia due to the linear relationship between maternal blood glucose and the risk of
complications, such as macrosomia. This table therefore reports the evidence in women with gestational
diabetes and any relevant indirect evidence from pregnant women with pre-existing diabetes, which is
included in the guideline recommendation, when no direct evidence was available.
ᵇ The guideline committee included data for the first, second, and third trimesters, all of which show no
statistically significant difference between treatment groups, underpinned by very low-quality evidence
What are the effects of self-management by regular blood glucose monitoring
in people with type 2 diabetes?[55]
EVIDENCE TABLES
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review)
that focuses on the above important clinical question.
View the full source guideline (https://www.nice.org.uk/guidance/ng28/evidence)
Evidence C * Confidence in the evidence is very low or low where GRADE has been performed
and there is a trade off between benefits and harms of the intervention.
Population: Adults with type 2 diabetes

Intervention: Self-monitoring blood glucose
Comparison: No self-monitoring blood glucose (including usual care and self-monitoring of urine glucose)
† ‡
Outcome Effectiveness (BMJ rating) Confidence in evidence (GRADE)
Haemoglobin A1c (HbA1c) Favours intervention Low

(follow up: 24-52 weeks)
Fasting blood glucose (mmol/ Favours intervention Low

L) (follow up: 26-52 weeks)
Post-prandial blood glucose Favours intervention Low

(mg/dL) at 26 weeks for
adults with type 2 diabetes
on diet, anti-diabetic, and/or
insulin medicines (follow up: 6
months)
Any hypoglycaemia from 26-52 Favours comparison Low

weeks (follow up: 6-12 months)
Severe hypoglycaemia from No statistically significant Low

26-52 weeks (follow up: 6-12 difference
months)
Adverse events at 6 months for No statistically significant Moderate

adults with type 2 diabetes on difference
oral anti-diabetes medicines
(follow up: 6 months)
Recommendations as stated in the source guideline

The guideline development group states: do not routinely offer self-monitoring of blood glucose levels for
adults with type 2 diabetes unless:
111
• the person is on insulin or
• there is evidence of hypoglycaemic episodes or

EVIDENCE TABLES
• the person is on oral medication that may increase their risk of hypoglycaemia while driving or
operating machinery or
• the person is pregnant, or is planning to become pregnant.
Note
The guideline development group noted that self-monitoring of blood glucose provides the potential for
tight glycaemic control which reduces the risk of diabetes-related complications. However, the impact on
hypoglycaemic events is important in determining the safety and acceptability in patients.
* Evidence levels
The Evidence level is an internal rating applied by BMJ Best Practice. See the EBM Toolkit (https://
bestpractice.bmj.com/info/evidence-tables/) for details.
Confidence in evidence
A - High or moderate to high

B - Moderate or low to moderate
C - Very low or low
† Effectiveness (BMJ rating)

Based on statistical significance, which demonstrates that the results are unlikely to be due to chance, but
which does not necessarily translate to a clinical significance.
‡ Grade certainty ratings
High The authors are very confident that the true

effect is similar to the estimated effect.
Moderate The authors are moderately confident that
the true effect is likely to be close to the
estimated effect.
Low The authors have limited confidence in the
effect estimate and the true effect may be
substantially different.
Very Low The authors have very little confidence in
the effect estimate and the true effect is
likely to be substantially different.
BMJ Best Practice EBM Toolkit: What is GRADE? (https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-
is-grade/)
Type 2 diabetes in adults References
Key articles
• National Institute for Health and Care Excellence. Diabetes in pregnancy: management from
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2021 [internet publication]. Full text (https://www.nice.org.uk/guidance/ng28)
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pubmed/30291106?tool=bestpractice.bmj.com)
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diabetes, 2018 – a consensus report by the American Diabetes Association (ADA) and the European
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link.springer.com/article/10.1007%2Fs00125-019-05039-w) Abstract (http://www.ncbi.nlm.nih.gov/
• National Institute for Health and Care Excellence. Type 2 diabetes in adults: management. November
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139
Contributors:
// Authors:
Amar Put tanna, MBChB, MRCP

Diabetes and Endocrinology Consultant
Good Hope Hospital, University Hospitals Birmingham NHS Trust, UK
DISCLOSURES: AP has received honoraria from Napp, Novo Nordisk, Sanofi, Lilly-Boehringer Ingelheim,
Daiichi-Sankyo, and AstraZeneca for presentation at meetings, conference registration or participating in
advisory boards.
Partha Kar, OBE, MBBS MD, FRCP

Consultant Endocrinologist
Portsmouth Hospitals University NHS Trust, National Specialty Advisor, Diabetes, NHS England, UK
DISCLOSURES: PK has sat on advisory boards and attended events reimbursed by Novo Nordisk, Eli Lilly,
and Sanofi.
// Acknowledgements:
Dr Amar Puttanna and Dr Partha Kar would like to gratefully acknowledge Dr Patrick J. O'Connor and Dr
JoAnn M. Sperl-Hillen, the previous contributors to this topic.
DISCLOSURES: PJO receives research funding from the National Institutes of Health on multiple projects
and is an author of a number of references cited in this topic. JMS-H is an author of a number of references
cited in this topic and is an inventor on a US patent for Disease Treatment Simulation, a simulation-
based technology developed without commercial support to educate health providers on chronic disease
management in a virtual environment.
// Peer Reviewers:
Vinod Patel, MD, FRCP, FHEA, MRCGP, DRCOG, MBChB, BSc (Hons), RCPathME
Professor, Diabetes and Clinical Skills
Warwick Medical School, University of Warwick, Hon Consultant in Endocrinology and Diabetes, Acute
Medicine, Medical Obstetrics, Diabetes and Endocrinology Centre, George Eliot Hospital NHS Trust,
Nuneaton, Clinical Director for Diabetes West Midlands Clinical Networks & Clinical Senate, NHS England
and NHS Improvement - Midlands, UK
DISCLOSURES: VP declares he has worked with most of the large pharmaceutical industry groups over
the years with the majority of the work being in education of healthcare professionals in diabetes care.
This includes Novo Nordisk, Eli Lily, MSD, BI, Sanofi, Napp, Internis, Takeda, and AZ. VP has been part
of advisory board work on occasions. VP has received conference arrangements and lecture fees. VP is a
trustee of the charity South Asian Health Foundation.
Gregory Lip, MD, FRCP, DFM, FACC, FESC, FEHRA

Price-Evans Professor of Cardiovascular Medicine
University of Liverpool, Senior Investigator, National Institute for Health Research, UK, Distinguished
Professor, Faculty of Medicine, Aalborg University, Denmark, Adjunct Professor, Yonsei University, Seoul,
South Korea
DISCLOSURES: GL has acted as a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and
Daiichi-Sankyo.

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Type 2 diabetes

Straight to the point of care

Last updated: Feb 22, 2022

Online resources 108

Evidence tables 109

Selected glucose-lowering drugs reduce all-cause and cardiovascular mortality.

Acanthosis nigricans involving the axilla

The presence of symptoms may indicate more overt hyperglycaemia.

• Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL), or

• A repeat confirmatory test on a subsequent day is required in asymptomatic patients.[45]

• In the presence of an underlying infection or other stressors

• Autoantibodies to glutamic acid decarboxylase 65 (GAD), islet cell antibodies (ICA),

Evaluation of disease and risks of macrovascular/microvascular

Initial and ongoing monitoring

• Immediately refer the patient to the local eye screening service[55]

• Offer and reinforce preventive lifestyle advice.[57]

History and exam

Other diagnostic factors

skin infections (common)

urinary tract infections (common)

blurred vision (common)

unintentional weight loss (uncommon)

acanthosis nigricans (uncommon)

Acanthosis nigricans involving the axilla

family history of type 2 diabetes

polycystic ovary syndrome

polyuria, polydipsia, or weight loss are present.

Other tests to consider

urine ketones positive in instances of

Condition Differentiating signs / Differentiating tests

Diabetes mellitus, type 1 • Tends to present in • Urine ketones are often

Latent autoimmune • Typical age of onset of • Positive for at least 1 of

Condition Differentiating signs / Differentiating tests

Monogenic diabetes • The two main forms of • Genetic testing in

Ketosis-prone diabetes • Presents with unprovoked • Absent islet cell auto-

Condition Differentiating signs / Differentiating tests

Diabetes, gestational • Only occurs during • Gestational diabetes is

• All adults aged 40 and above (except pregnant women)

• Ongoing self-management education by a diabetes education nurse or dietitian promotes diabetes

• About 80% of adults with type 2 diabetes have concurrent dyslipidaemias or

of your patient. Take into account the patient’s:[55]

Diet, physical activity, and sleep

Encourage the patient to:[55]

• Include high-fibre, low-glycaemic-index sources of carbohydrate in their diet, such as fruit,

In terms of physical activity, encourage the patient to:

• Reduce sedentary behaviour and be more physically active[96]

Cardiovascular risk management

• The prevalence of hypertension is >60% in patients with type 2 diabetes.[42]

In the UK, NICE recommends a stepwise approach to pharmacological treatment of hypertension in

For initial treatment, give:

• An ACE inhibitor or an angiotensin-II receptor antagonist

• If an ACE inhibitor is not tolerated, use an angiotensin-II receptor antagonist instead

If hypertension remains uncontrolled on first-line therapies:

• Discuss, and support, adherence with antihypertensive medication

• An ACE inhibitor or an angiotensin-II receptor antagonist, and

• Discuss adherence and timing of dose

ESC/EASD guidelines categorise cardiovascular risk in patients with diabetes as:[42]

• Very high risk

• Patient with diabetes and any one or more of:

• Established cardiovascular disease

• At moderate cardiovascular risk: an LDL-cholesterol target of <2.6 mmol/L (<100 mg/dL)

mmol/L (<100 mg/dL)