Diabetes Mellitus

Karishma Jeeboo, RPh,

PharmD.
 By the end of this presentation, students should be able to:

Define diabetes
Learning Outcomes
Discuss the prevalence and epidemiological data for diabetes

Determine the classification of diabetes

Identify risk factors for and complications of diabetes

Discuss Pre-Diabetes and Screening

Discuss the non-pharmacologic and pharmacologic management of diabetes

types 1 and 2.

Discuss the pharmacist's role and strategies for managing diabetes and
preventing progression (CVD and CKD).
Introduction
Chronic metabolic disturbance characterized by fasting and/or
postprandial hyperglycemia.

absolute or relative lack of insulin, resistance to the action of

insulin, or both.

Minor degrees of blood glucose abnormalities (dysglycemia), even

those not meeting the diagnostic threshold for diabetes mellitus, are
still associated with increased cardiovascular risk.
Introduction
Long-term diabetes mellitus may lead to complications that involve the
small blood vessels (microangiopathy), large blood vessels
(macroangiopathy) and nerves (neuropathy) of multiple organs and systems.

Because diabetes is associated with significant dysfunction of numerous

metabolic pathways, clinicians must pay close attention to factors such as
hypertension and dyslipidemia in addition to blood glucose.
 Facts and Figures
• Over 90% of people with diabetes have type 2 diabetes
• 10.5% of the adult population (20-79 years) has diabetes, with almost
half unaware that they are living with the condition.
• The total number of people living with diabetes is projected to rise
to 643 million by 2030 and 783 million by 2045.
• By 2045 - 1 in 8 adults, an increase of 46%.
• 3 in 4 adults with diabetes live in low- and middle-income countries

International Diabetes Federation (IDF), 2021

 Facts and Figures
• Diabetes is a major cause of blindness, kidney failure, heart attacks,
stroke and lower limb amputation.
• In 2019, diabetes and kidney disease due to diabetes caused an
estimated 2 million deaths.
• Prevalence has been rising more rapidly in low- and middle-income
countries than in high-income countries.
• From 2009 to 2019, the number of diabetes-related hospitalizations
due to amputation doubled.
• A growing global burden for individuals, families, and countries.
World Health Organisation, April 2023
 Type 1 diabetes mellitus (T1DM) is due to autoimmune beta
cell destruction resulting in an absolute deficiency of insulin.

T1DM usually presents with acute metabolic symptoms of

relatively short duration in a child, adolescent or young adult.

Classification If untreated, ketoacidosis may occur.

T1DM is not common after 30 years of age, some older

individuals with type 2 diabetes mellitus may develop markers
of autoimmunity and progress quickly to an insulin-
dependent state (latent autoimmune diabetes of adulthood).
 Type 2 diabetes mellitus (T2DM) manifests primarily as
insulin resistance along with some degree of insulin
deficiency.
Over time, insulin deficiency worsens, resulting in more
prominent hyperglycemia.

Discovered incidentally or is diagnosed in adults who are

Classification often obese and have nonspecific symptoms.

Rising prevalence – particularly certain ethnic groups

Diagnosed more frequently and earlier in obese children

and adolescents.
 Gestational diabetes is defined as onset or
recognition of glucose intolerance in pregnancy.

Classification Other specific causes of diabetes mellitus include

monogenetic syndromes such as maturity-
onset diabetes of the young (MODY) or are a
result of pancreatic diseases (Type 3c), infectious
agents, drugs, pancreatic surgery or other
diseases leading to carbohydrate intolerance.
Risk Factors for Diabetes Mellitus
• Age ≥40 years
• First-degree relative with T2DM – mother, father, brother, sister
• High-risk population, e.g., Indigenous, Hispanic, South Asian, Asian, African, low
socioeconomic status
• History of pre-diabetes
• History of gestational diabetes mellitus
• History of delivery of a macrosomic infant
• Presence of end-organ damage associated with diabetes, e.g., cardiovascular,
microvascular
Risk
Presence of vascular risk factors:

• abdominal obesity/visceral adiposity[a]

• Decreased HDL cholesterol <1 mmol/L in males or <1.3 in

Factors females[a]
• hypertension[a]
• being overweight[a]
• Elevated triglycerides ≥1.7 mmol/L[a]
• Smoking

Presence of associated diseases:

• acanthosis nigricans[a]
• cystic fibrosis
• history of pancreatitis
• HIV infection
• hyperuricemia/gout
• non-alcoholic steatohepatitis
• obstructive sleep apnea
• polycystic ovary syndrome[a]
• psychiatric disorders, e.g., bipolar disorder, depression,
schizophrenia
Examples of Drugs That Can Cause Dysglycemia
• Beta-blockers, e.g., atenolol, metoprolol, propranolol (can result in consistently elevated fasting blood
glucose levels); (Carvedilol and Nebivolol not associated with hyperglycemia)
• Corticosteroids, e.g., prednisone
• Diazoxide
• HMG-CoA Reductase Inhibitors (statins)
• Immunosuppressive agents (Calcineurin Inhibitors (CNIs), e.g., sirolimus, tacrolimus, cyclosporine
• Interferon alfa
• Isoniazid
• Niacin
• Pasireotide
• Pentamidine
• Protease inhibitors, e.g., amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir,
nelfinavir, ritonavir, saquinavir, tipranavir
• Second-generation antipsychotic agents/Atypicals, e.g., clozapine, olanzapine, paliperidone,
quetiapine, risperidone (intermediate) (Clozapine and olanzapine are the riskiest)
• Thiazide or loop diuretics, e.g., chlorthalidone, furosemide, hydrochlorothiazide
• Statins
• Quinolones – Gemifloxacin (commonly implicated; also associated with hypo); Levofloxacin (weak)
Servier Medical Art
Poll Question #1
All of the following are likely to be associated with insulin resistance
except:
A. Abdominal obesity
B. Hypertension
C. Smoking
D. PCOS
 • Term used for individuals
whose glucose levels do not
meet the criteria for diabetes
yet have abnormal
carbohydrate metabolism

Criteria defining prediabetes

• FPG 100 mg/dL (5.6 mmol/L) to
125 mg/dL (6.9 mmol/L) (IFG)
OR
Pre-Diabetes • 2-h PG during 75-g OGTT 140
mg/dL (7.8 mmol/L) to 199
mg/dL (11.0 mmol/L) (IGT)
OR
• A1C 5.7–6.4% (39–47
mmol/mol)

ADA Guidelines
 Criteria for Screening in
Asymptomatic Adults

Standards of Care in Diabetes, 2023, American Diabetes Association

Risk-Based Screening for Type 2 Diabetes or Prediabetes in
Asymptomatic Children and Adolescents in Clinical Setting

Standards of Care in Diabetes, 2023, American Diabetes Association

Diagnosis of Prediabetes and Diabetes
Investigations
Diabetes mellitus may present in a variety of settings:

asymptomatic; incidental discovery through routine laboratory screening

nonspecific signs and symptoms such as fatigue, lassitude, weight changes

presence of diabetic macrovascular or microvascular complications including

neuropathy, kidney disease, erectile dysfunction, vision changes
acute metabolic symptoms such as polyuria, polydipsia, weight loss,
diabetic ketoacidosis
Poll Question #2
The target blood pressure for patients with diabetes is ≥ 130 mmHg.
A. True
B. False
Goals of Therapy
• Control Symptoms
• Establish and maintain
glycemic control while
avoiding hypoglycemia
• Prevent or minimise the risk
of acute and chronic
complications
• Achieve optimal control of
associated risk factors such as
hypertension, obesity and
dyslipidemia
Therapeutic Choices
Non-Pharmacologic and Pharmacologic
 Non-pharmacologic Choices
• Self-management education is vital in making patients full participants
in the diabetes health-care delivery team and ensuring that they can
effectively and safely manage their disease.
• Diabetes self-management education and support (DSMES) – First
World
Education
A well-structured educational program should include:
• a basic understanding of diabetes
• the role of diet, exercise and medications
• how and when to self-monitor blood glucose and why it is necessary
• the management of sick days
• recognition and treatment of hypoglycemia
• knowledge of the major side effects of medications and possible
medication adjustments in response to changes in diet and activity
• care of the feet
• awareness of the risk of heart disease and the importance of risk-factor
control, including body weight
 Nonpharmacologic Choices
Individualized nutritional management.
• Provide counselling by a registered dietitian
and include information on nutrients from
all the basic food groups.
• If they are overweight, reduce total caloric
consumption in patients with T2DM to
decrease weight and improve metabolic
control.
• For patients on insulin, tailor the distribution
of food intake into meals and snacks
according to the individual's preference,
lifestyle and medications.
• In patients with T1DM, carbohydrate intake
and insulin dose must be linked.
• Options include advising patients to fix
carbohydrate consumption or count the
amount of carbohydrate ingested and adjust
the insulin dose accordingly.
Nonpharmacological Choices
• Self-monitoring of blood glucose (SMBG) is an essential component of
normalizing blood glucose for the majority of patients
with diabetes mellitus.
• It allows appropriate recognition of low blood glucose levels and
provides immediate feedback about the effects of therapy.
SMBG
• For patients treated with insulin, SMBG is especially important.
• In these patients, individualize self-monitoring strategies and take
both pre- and postprandial measurements.
• A minimum of 3 blood sugar measurements per day should be
performed for those on basal-bolus insulin regimens.
• Duration of blood glucose monitoring in patients on oral therapy must
be individualized and should be based on factors
SMBG
• Capillary blood glucose testing has been the usual technique used for
SMBG.
• Other devices are available that measure the glucose concentration in
interstitial fluid to provide continuous glucose monitoring (CGM) or
flash glucose monitoring (FGM).
• These technologies represent alternatives to the traditional SMBG for
some people, particularly those who may have labile glucose levels or
require frequent SMBG.
 Physical Activity
• Physical activity will improve cardiovascular function, enhance insulin
sensitivity, and lower blood pressure and lipid levels.
• Physical activity also helps improve glycemic control in people with
T2DM.
• Encourage aerobic exercise totaling ≥150 minutes per week along with
resistance training at least twice a week.
• It is imperative to educate patients treated with insulin about the
effect of exercise on blood glucose and how to adjust the insulin dosage
accordingly.
Physical Activity
• Predictable intensity and duration allow individuals to understand
how blood glucose levels will change immediately following the
exercise.
• Typically, blood glucose levels will decrease after moderate-intensity
exercise but may increase after intense activity (likely a stress
response).
• Teach patients how to time their meals and/or regulate food
consumption to ensure the safety of the prescribed exercise regimen
 Physical Activity
• Individuals with diabetes and overweight or obesity may benefit from
modest or larger magnitudes of weight loss.
• Relatively small weight loss (approximately 3–7% of baseline weight)
improves glycemia and other intermediate CV risk factors. (A)
• Larger, sustained weight losses (>10%) usually confer greater benefits,
including disease-modifying effects and possible remission of type 2
diabetes, and may improve long-term CV outcomes and mortality. (B)

ADA Standards of Care, 2023

 Treatment Options for Overweight
and Obesity in Type 2 Diabetes

ADA Standards of Care Guidelines, 2023

Immunizations
• Immunize patients with diabetes to reduce the risk of complications
and hospitalization.
• In adults, annual influenza immunization and a one-time
pneumococcal vaccination are recommended.
• People with diabetes should be prioritized and offered SARS-CoV-2
vaccines.
Pharmacological Choices
Type 1 Diabetes
• Insulin may be administered by syringe, pen or continuous
subcutaneous insulin infusion (CSII or insulin pump).
• Although insulins from animal sources are still marketed, most
patients use human insulin and insulin analogues since these agents
cause less antibody generation and related adverse reactions (e.g.,
hypersensitivity, insulin resistance).
• Human insulins are produced by recombinant DNA technology and
have an amino acid sequence identical to endogenous human insulin.
 Insulins
• Insulin analogues are slightly modified human insulin molecules.
• The rapid-acting insulin analogues (RAIAs) insulin aspart, insulin
glulisine and insulin lispro allow for more flexibility to control postprandial
glucose because of their faster onset of action compared with short-acting
insulins.
• A concentrated 200 units/mL version of insulin lispro is available, reducing
the volume needed to be injected, which is useful in those requiring large
doses with each meal (>50 units).
• There is also faster-acting insulin aspart, which provides a more rapid onset
of action.
• This product may be administered up to 2 minutes prior to a meal and, if
necessary, up to 20 minutes after starting the meal.
 Insulin
• The long-acting insulin analogues (LAIAs) insulin detemir and insulin
glargine appear to produce more predictable effects than intermediate-
acting human insulin (NPH) and are associated with fewer episodes of
hypoglycemia, particularly nocturnal hypoglycemia.
• In a meta-analysis, patients with T1DM who used LAIAs for a year had
significantly fewer episodes of nocturnal hypoglycemia compared to
using NPH (NNT = 20 to prevent 1 episode).
• Insulin glargine is available in different formulations, including a
concentrated 300 units/mL product.
Insulin Regimens
• This concentrated formulation appears to have a longer duration of
action, has no peak effect and further reduces hypoglycemia
compared to insulin glargine 100 units/mL.
• Insulin degludec is a long-acting basal insulin available in 100
units/mL and 200 units/mL strengths.
• Insulin degludec has a long duration of action of approximately 42
hours.
• Compared with insulin glargine 100 units/mL, it was shown to be as
effective in controlling glucose, with a 26% relative risk reduction in
nocturnal hypoglycemia
Insulin Regimens
• The Diabetes Control and Complications Trial (DCCT) showed that
intensive treatment regimens control blood glucose more effectively
than conventional regimens and reduce the risk of long-
term diabetic microvascular complications (retinopathy, nephropathy,
neuropathy).
• Follow-up data from the trial demonstrate a long-term benefit of
intensive therapy on the risk of cardiovascular events and mortality.
• Newly diagnosed patients and those with poor glycemic control on
conventional regimens should be offered the option of
intensive diabetes management consisting of multiple-dose insulin
(MDI) regimens.
Insulin Regimens
• Assess each patient to determine whether an intensive regimen is
suitable.
• Less intensive regimens - the frail elderly, unmotivated patients or
those who lack awareness of severe hypoglycemia.
• In clinical practice, RAIA, in combination with LAIA is preferred over
regular insulin in order to minimize the risk of hypoglycemia and
improve HbA1c and postprandial glucose levels.
Insulin Regimens
• Most lean patients with T1DM require approximately 0.5 units of insulin per
kilogram of body mass.
• In the first few months following a T1DM diagnosis, patients may experience
periods where the requirement for insulin is decreased or transiently eliminated.
• This phenomenon is known as the honeymoon phase.
• Initiate insulin therapy judiciously in order to minimize the risk of hypoglycemia
and adjust the dose every 2–3 days according to blood glucose results.
• Regular home monitoring allows patients to adjust the dose of insulin in response
to abnormal blood glucose levels, effects of diet and exercise, and changing blood
glucose patterns.
• Optimal blood glucose control is achieved by matching the timing of insulin
injections with caloric intake: regular insulin is given approximately 30 minutes
before meals and RAIAs should ideally be administered 0–15 minutes prior to
starting a meal.
Insulin Regimens
• The use of insulin pumps and regimens involving multiple doses of
RAIA improves the stability of postprandial glucose levels.
• May also diminish the frequency and severity of hypoglycemia,
especially early nocturnal hypoglycemia.
• Insulin pumps can achieve a tighter and more reproducible degree of
glycemic control, particularly in those with a high initial HbA1c, but at
a significantly increased expense for the patient.
 Insulin Regimens in Type 1 and Type 2 Diabetes Mellitus
Rapid- or Short-Acting (Bolus) Intermediate- or Long-Acting (Basal) Comments
Intensive: Basal-Bolus (Multiple-Dose Insulin Regimens)
Insulin aspart, glulisine or lispro before each meal Insulin degludec, detemir, glargine 100 units/mL or Recommended in all T1DM when not using an insulin
Alternatively regular human insulin may be used glargine 300 units/mL once daily at supper or bedtime pump, and in some T2DM.
(preferred); may use detemir or glargine 100 units/mL Requires glucose monitoring and dosing calculations
twice daily in 2 equal doses with each meal.
Alternatively NPH once or twice daily may be used

Intensive: Continuous Subcutaneous Insulin Infusion (Insulin Pump)

Rapid-acting insulin delivered by an electronic infusion None
set: insulin aspart or lispro recommended; basal and
boluses delivered according to programmable settings
Basal Insulin Only
None
Insulin degludec, detemir, glargine 100 units/mL or
glargine 300 units/mL once daily preferred; NPH can
be used as an alternative
Expensive and frequent testing required.
Carbohydrate counting and insulin-correction ratios
required for dosing.
DKA may occur quickly after discontinuation, tubing
block or pump failure.
Use in T2DM only.
Variable initiation strategies, including starting with 5–
10 units at bedtime and titrating to a fasting blood
glucose <7 mmol/L.

Basal-Plus (for patients desiring fewer injections)

Insulin aspart, glulisine or lispro before the single
largest daily meal
Alternatively regular human insulin may be used
Insulin degludec, detemir, glargine 100 units/mL or Use in T2DM only.
glargine 300 units/mL once daily. Alternatively, if NPH Could substitute a premixed insulin product given
preferred, administer with breakfast and supper twice daily.
Titrate to a fasting blood glucose <7 mmol/L and to 2
hr postprandial blood glucose <10 mmol/L.
Insulin Activity
Insulin Activity
Insulin Therapies
Adverse Effects of Insulin Therapy
• Allergic reactions, such as urticaria, angioedema, rashes and local
erythema, are rare with human insulin.
• If they do occur, switching to a different insulin manufacturer may
help.
• Immune-mediated insulin resistance due to the production of anti-
insulin antibodies is also rare with human insulin.
Pharmacotherapy
Type 2 Diabetes Mellitus
T2DM
• Initial management of patients with T2DM generally depends on the
HbA1c
FPG/Preprandial Glucose
Age HbA1c 2-h PPG
(mmol/L)
(years) Diabetes Type (%) (mmol/L)
T2 ≤6.5[a]

4–7 5–10
>18 T1,T2 ≤7
4–5.5 if goal HbA1c not reached 5–8 if goal HbA1c not reached

T1, T2 7.1–8.5[b]

T1 ≤7.5 4–8[c] 5–10

≤18
T2 ≤7 No recommendation No recommendation
Glycemic
Targets –
Individualized
Antihyperglycemic Agents
• In all patients who have been started on antihyperglycemic agents,
aim to reach the desired HbA1c target within 3–6 months through
dosage titration or addition of other agents.
• Typically, the higher the baseline HbA1c, the greater the reduction in
HbA1c that can be achieved with treatment.
• After metformin, the drug chosen as the second-line agent should be
individualized, taking into consideration presence of clinical
cardiovascular disease, kidney function, hypoglycemia and weight
concerns, cost, and insurance coverage, amongst others.
Antihyperglycemic Agents
• Vascular protection is a significant goal in the management
of diabetes.
• In 2008 the FDA began requiring cardiovascular safety trials as part of
the approval process for new medications for T2DM.
• NEW Guidelines now recommend that the results of cardiovascular
safety trials be considered when selecting medications for the
treatment of T2DM
Antihyperglycemic Agents
Biguanides
• Metformin is generally considered the first choice for patients with a
new and uncomplicated diagnosis of T2DM.
• It decreases hepatic glucose production and may lower glucose
absorption and enhance insulin-mediated glucose uptake.
• It is not associated with weight gain, it lowers HbA1c by
approximately 1–1.5% and the risk of hypoglycemia is low when it is
used as monotherapy.
• However, it can potentiate the hypoglycemic effects of insulin and
sulfonylureas.
Metformin
• Metformin is thought to improve CV risk.
• Metformin is also routinely held preoperatively and when imaging-
contrast agents (2-3 days) are being given due to the possibility of
acute renal failure, which may increase the risk of lactic acidosis.
• May be associated with biochemical vitamin B12 deficiency (long-
term)
• metformin should be taken with a meal to limit gastrointestinal side
effects.
• Metformin therapy for the prevention of type 2 diabetes should be
considered in adults with high risk of type 2 diabetes (A).
Metformin
• eGFR >45 mL/minute/1.73 m2: No dosage adjustment necessary;
monitor renal function at least annually. More frequent monitoring
(every 3 to 6 months) and a maximum dose of 2 g/day has been
recommended for patients with eGFR >45 to <60 mL/minute/1.73 m2
• If eGFR falls between 30 and <45 mL/minute/1.73 m2 during therapy:
Consider benefits/risks of continuing therapy. If continuing therapy, a
dosage reduction of 50% (maximum: 1 g/day) and monitoring of renal
function every 3 months is recommended.
• eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
 Metformin
• Although the use of metformin has traditionally been discouraged due to
the perceived risk of lactic acidosis in patients with heart failure, renal or
hepatic disease, or hypoxemic states, a Cochrane review of 347 studies
comparing over 70 000 subjects found no increase in the rate of lactic
acidosis among patients receiving metformin compared with controls
receiving other antihyperglycemic agents.
• Metformin and cimetidine – MALA (Metformin-associated lactic acidosis.
• Clinical presentation of lactic acidosis is often nonspecific flu-like
symptoms and may include altered consciousness, heavy, deep
(Kussmaul) breathing, and abdominal pain and thirst.
• Diagnosis is usually made by laboratory confirmation.
Alpha-glucosidase Inhibitors
• Acarbose and miglitol inhibit intestinal alpha-glucosidases, resulting in
delayed digestion of starches and disaccharides and reduced
postprandial glucose levels.
• They do not significantly inhibit intestinal lactase.
• Acarbose does not cause hypoglycemia but can increase the risk of
hypoglycemia when combined with insulin or insulin secretagogues,
and causes significant GI effects.
• In addition, it requires TID dosing (before meals) and lowers HbA1c by
≤1%.
 Thiazolidinediones (TZDs)
• Pioglitazone and rosiglitazone are agonists at peroxisome proliferator-
activated receptor gamma (PPARG) receptors located on the cell
nucleus.
• These medications influence gene expression in the cell leading to
enhanced insulin sensitivity and lower levels of blood glucose and
circulating insulin.
• The TZDs also exhibit increased peripheral glucose uptake, enhanced fat
cell sensitivity to insulin and decreased hepatic glucose output.
• The risk of hypoglycemia with TZDs is very low as monotherapy
• however, they may enhance the hypoglycemic effects of insulin and
SUs.
Thiazolidinediones (TZDs)
• The mean decrease in HbA1c is 1–1.5%.
• Individual TZDs may differ in their effects on serum lipids.
• Both agents are associated with weight gain due to increased
subcutaneous fat deposition, fluid retention and edema, which is
likely the cause of the increased incidence of heart failure in patients
receiving TZDs.
Insulin Secretagogues: Sulfonylureas
• The sulfonylureas (SUs) chlorpropamide (1st Gen), gliclazide, glimepiride,
• glyburide and tolbutamide stimulate both basal and meal-stimulated
insulin release.
• HbA1c can be lowered by 1–1.5%.
• Significant differences exist between agents in regard to effectiveness,
hypoglycemia risk, postprandial correction of glucose and weight gain.
• First-generation SUs (chlorpropamide, tolbutamide) are typically not used
due to their pharmacokinetic profile and higher affinity for drug
interactions.
 Insulin Secretagogues: Sulfonylureas
• Glyburide is an inexpensive second-generation SU.
• Glyburide is associated with a greater risk of hypoglycemia, especially in
elderly patients or those with renal impairment.
• Though more common with glyburide, hypoglycemia and weight gain can
occur with any of these agents to varying degrees.
• The hypoglycemic effect of glipizide may be delayed slightly if taken with
a meal versus 30–60 minutes before a meal, although haemoglobin A1c
(A1C) values are unaffected.
• SUs are considered useful as either add-on therapy or, less often as
monotherapy when metformin is contraindicated.
Glucagon-Like Peptide-1 Agonists
• Glucagon-like peptide-1 agonists mimic the actions of GLP-1, an
endogenous “incretin” hormone.
• GLP-1 is secreted in response to food ingestion by endocrine cells
found in the gastrointestinal tract.
• When GLP-1 agonists are administered, they increase GLP-1 action by
approximately 5-fold.
• They lower HbA1c to a greater extent than DPP-4 inhibitors but cause
more nausea upon initiation of therapy and can cause vomiting as
well.
Glucagon-Like Peptide-1 Agonists
Examples:
• Exenatide (Byetta)
• Exenatide XR (Bydureon)
• Liraglutide (Victoza)
• Dulaglutide (Trulicity)
• Lixisenatide (Adlyxin)
• Semaglutide (Ozempic)
• Oral Semaglutide (Rybelsus)

• Administration
• Subcutaneous injection (and oral)
• Twice daily, once daily, or once weekly
 Glucagon-Like Peptide-1 Agonists

Exenatide (Byetta) Lixisenatide (Adlyxin) Liraglutide (Victoza) Exenatide XR (Bydureon) Dulaglutide Semaglutide
(Trulicity) (Ozempic)
Dose 5 mcg SC twice daily x 1 10 mcg SC once daily; 0.6 mg SC once daily x 1 2 mg SC once weekly 0.75 mg SC once 0.25mg SC once
month, 10 mcg BID if can ↑to 20 mcg week, 1.2 x 1 week, then weekly, can ↑ to weekly, can ↑ to 1
tolerated 1.8 1.5 mg mg

Admin Twice daily 30–60 min Once daily 1 hr before Once daily Once weekly Once weekly Once weekly
before meal breakfast
Delivery Multi-use pen (5 mcg, 10 Multi-use pen (10mcg, Multi-use pen (three Single-use pen (2 mg, Single-use pen Single-use pen
mcg) 20 mcg) doses in one pen) requires reconstitution) (0.75 mg, 1.5 mg)(0.25mg-0.5mg or
1mg)
Storage Active pen room temp; Active pen room temp; Active pen room temp; Refrigerate; or room temp Refrigerate; or Active pen room
refrigerate others refrigerate others refrigerate others for 28 days; room temp 15 room temp for 14 temp or
min before reconstitution days refrigerate;
refrigerate others
Renal < 30 not rec < 30 not rec None < 30 not rec None None
dosing 30–50 use caution 30–50 use caution
Dipeptidyl Peptidase-4 Inhibitors
• Endogenous glucagon-like peptide-1 (GLP-1) is rapidly degraded by
the enzyme dipeptidyl peptidase-4 (DPP-4) to an inactive state.
• DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin and sitagliptin)
increase the availability of GLP-1 as well as other potentially active
peptides involved in glucose homeostasis.
• Overall, they lower HbA1c by ≤1% and are well tolerated medications
with low risk of hypoglycemia.
Sodium-Glucose Cotransporter 2 Inhibitors
• The newest class of antihyperglycemics are the sodium-glucose
cotransporter 2 (SGLT2) inhibitors
• Prevent glucose reabsorption in the kidneys, leading to increased
excretion of urinary glucose and a lowering of blood glucose.
• Some weight loss is associated with SGLT2 inhibitors
• SGLT2i - Canagliflozin (Invokana®), dapagliflozin (Farxiga®),
empagliflozin (Jardiance®), ertugliflozin (Steglatro®), sotagliflozin (in
development)
Sodium-Glucose Cotransporter 2 Inhibitors
• Small decrease in blood pressure, which may be a benefit in many,
and a low risk of hypoglycemia.
• CV and CKD benefits in patients
• Side effects of note with this class of medications include mycotic
genital infections, volume depletion–related adverse effects, urinary
tract infections and some reports of diabetic ketoacidosis.
• Clinical trials have shown lower rates of kidney disease progression.
• Expensive
 Renal Function and Dosing of SGLT2i
eGFR Range Canagliflozin Dapagliflozin Empagliflozin

>60 ml/min/1.73m2 100-300 mg/d 5-10 mg/d 10 – 25 mg/d

45-60 ml/min/1.73m2 Do not exceed 100mg/d Do not initiate 10 – 25 mg/d

<45 ml/min/1.73m2 Do not initiate Do not initiate Do not initiate

<30 ml/min/1.73m2 Contraindicated Contraindicated Do not initiate

Adjustments during Not recommended when Not recommended when Discontinue when eGRF
therapy eGRF declines persistently eGRF declines persistently falls persistently below 45
below 45 ml/min/1.73m2 between 30-60 ml/min/1.73m2
ml/min/1.73m2
Insulin Regimens for Type 2 Diabetes Mellitus
• Due to the progressive nature of T2DM, noninsulin antihyperglycemic
agents gradually lose their effectiveness over time.
• Insulin remains an important option for patients because of its
powerful effects on lowering HbA1c.
• Generally, clinicians would start patients on bedtime basal insulin if
they are not controlled on orals.
• Insulin does not directly alter CV risk.
Insulin Regimens
• Insulin must be initiated in patients with T1DM at the time of
diagnosis and should be considered in those with T2DM who present
with marked hyperglycemia and HbA1c ≥1.5% above their target
(typically >8.5%).
• In newly diagnosed T2DM patients with HbA1c <1.5% above their
target, lifestyle modifications alone may be appropriate as a first step.
• However, if glycemic goals are not reached within 3 months,
pharmacotherapy should be initiated
 Role of the
Pharmacist
and Strategies
for Managing
Patients

Decision cycle for person-centered glycemic management in type 2 diabetes. Adapted from Davies MJ, Aroda VR, Collins BS, et al.
Diabetes Care 2022;45:2753–2786.
Role of the Pharmacist
• Use person-centred, nonjudgmental language that fosters
collaboration between individuals and HCPs, including person-first
language (e.g., “person with obesity” rather than “obese person”).
• Measure height and weight and calculate BMI for patients – online
resources.
• Nutrition, physical activity, and behavioural therapy (B)
• Medication regimen and medication-taking behaviour should be
reevaluated at regular intervals (every 3–6 months) and adjusted as
needed to incorporate specific factors that impact the choice of
treatment
Role of the Pharmacist
• Enable collaborative and multidisciplinary team-based care. (A)
• Complementary Telepharamcy/Telehealth/Telemedicine (B)
• Encourage appropriate vaccinations
• Essential to achieving diabetes treatment goals are DSMES, medical
nutrition therapy (MNT), routine physical activity, tobacco cessation
counselling when needed, health behaviour counselling, and
psychosocial care.
• HCPs should refer people with diabetes for individualized MNT
provided by a registered dietitian
Role of the Pharmacist
• Referral to a specialist (ophthalmologist or optometrist) for an eye
examination
• Advise all individuals not to use cigarettes and other tobacco products
or e-cigarettes (Smoking Cessation programmes)
References
• https://www.who.int/news-room/fact-sheets/detail/diabetes
• https://idf.org/about-diabetes/facts-figures/
• https://diabetesjournals.org/care/issue/46/Supplement_1
• https://diabetesjournals.org/view-
large/figure/4514217/diaclincd23as01t1.tif
• https://diabetesjournals.org/clinical/article/41/1/4/148029/Standard
s-of-Care-in-Diabetes-2023-Abridged-for
• https://diabetesjournals.org/spectrum/article/24/4/234/31830/Drug
-Induced-Glucose-Alterations-Part-2-Drug
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