DIABETES

Disease overview
management
Medications
DR SACHIN R PATIL
OPERATION HEAD
KOLHAPUR RIC
Diabetes mellitus
Definition: a syndrome of disordered metabolism due to a
combination of hereditary and environmental causes.
Classification:
Type 1: Lack of insulin.
Type 2: Cells resistance to insulin
Signs & symptoms:
• Very thirsty
• Feeling tired
• Using the toilet often to urinate
• Constant hunger
• High level of glucose in urine & in fasting blood
People at high risk of diabetes
Factors associated with increased risk for diabetes include:
 Increasing age
 Metabolic syndrome
 Impaired glucose tolerance
 Polycystic ovary syndrome
 History of gestational diabetes or having a baby over 4 kg
 Family history of diabetes
 Physical inactivity
 Increased BMI
 Central obesity
 Hypertension
 Adverse lipid profile
 Elevated LFTs
 Patients taking some drugs e.g. prednisone or anti-psychotic drugs
(haloperidol, chlorpromazine, and newer atypical anti-psychotics).
 People at high risk of diabetes

Risk Factor Defining Level People with the metabolic syndrome

are at increased risk of diabetes,
Waist Men ≥ 100 cm
circumference* Women ≥ 90 cm cardiovascular disease.
Triglycerides ≥ 1.7
mmol/L(150.57mg)
HDL cholesterol Men < 1.0
mmol/L(38.66mg)
Women < 1.3
mmol/L(50.27mg)
Blood pressure SBP ≥ 130 or DBP ≥ 85

Fasting glucose ≥ 6.1

mmol/L(109.9mg/dl)
People with symptomatic
hyperglycaemia
Symptomatic hyperglycaemia may have an acute onset, usually in younger people with type 1
diabetes, or a more insidious onset, usually in older people with type 2 diabetes. The usual
symptoms of hyperglycaemia are thirst, polyuria and weight loss but hyperglycaemia can also cause
fatigue, lack of energy, blurring of vision or recurrent infections, such as candida.

For people with symptomatic hyperglycaemia,

a single fasting glucose of ≥ 7.0 mmol/L (126.12mg/dl)
OR
a random glucose of ≥ 11.1 mmol/L (200mg/dl)
is diagnostic of diabetes.
Target level for HbA1C
 Any sustained reduction of HbA1C is worthwhile
because there appears to be a direct relationship
between cardiovascular risk and HbA1C.
 The goal is to achieve an HbA1C as low as
possible, preferably less than 7.0%, without
causing unacceptable hypoglycaemia.
 HbA > 8 mmol/L is a sign of inadequate control
1C
for most people.
Antidiabetic drug and their action
Goal
To understand the use and side effects of anti-
diabetic medications and be able to educate
patients.

We have to Change this patern of rx

 Nine to Know
 Brand & Generic Name
 Mechanism of action
 Therapeutic effect
 Relevant pharmacokinetics and pharmacodynamics
 Dosing by route
 Adverse reactions and contraindications
 Monitoring parameters
 Drug-drug and drug food interactions
 Comparisons between agents w/in the same class of drugs
Contraindications/Cautions/Adverse
Reactions
 Adverse Reactions
 Unwanted side effects: need to warn patient
 Cautions
 Warnings for clinicians to be aware when using
medication.
 Contraindications
 Conditions which will render the medication absolutely
unusable in that patient population
 Type 2 Diabetes
High blood glucose

Impaired GI motility

1. Defective beta cell function

• Diminished phase 1 insulin release
• Delayed phase 2 insulin release
2. Overproduction of glucagon

1. Tissues less sensitive to insulin

2. Liver produces excess glucose
Treatment of Type 2 Diabetes
Diagnosis

Therapeutic Lifestyle Change

Monotherapy

Combination Therapy - Oral Drugs Only

Combination Therapy - Oral Drug with Insulin

 Combination Therapy
for Type 2 Diabetes
Sulfonylureas

Alpha-glucosidase
Biguanides Inhibitors

Meglitinide Thiazolidinediones

Insulin
Combination Therapy for
Type 2 Diabetes

Fixed Combination Pills

Sulfonylurea + Biguanide
Glyburide + Metformin - Glucovance
Glipizide + Metformin - Metaglip

Thiazolidinedione + Biguanide
Rosiglitazone + Metformin - Avandamet
 Efficacy of Monotherapy with Oral
Diabetes Agents
Drug Fasting Plasma A1C
Glucose Reduction Reduction
(mg/dl) (%)
Thiazolidinedione 35-40 0.5-1.0

Sulfonylurea 60-70 1.0-2.0

Biguanide 60-70 1.0-2.0

Meglitinide 60-70 1.0-2.0

Alpha-glucosidase 20-30 0.5-1.0

inhibitor
 Biguanides
Metformin Glucophage 500, 850, 1000 mg tablets
(Glucophage XR) 500, 750 mg XR tablets

Indication
 
Type II Diabetes Mellitus, Antipsychotic-induced weight gain

MOA
 
Decrease hepatic glucose production, decrease intestinal absorption of
glucose and increase insulin sensitivity therefore increasing peripheral
glucose uptake
 
Where does it work?
 Biguanides (cont)
Patient Info
Upset stomach/dyspepsia – take with food
Metallic taste
Minimal Weight Loss
Alcohol may increase likelihood of lactic acidosis
Does not cause hypoglycemia
 Biguanides (cont)

Cautions/Severe Adverse Reactions

Black Box Lactic Acidosis: D/C immediately and notify
practitioner if: myalgia, malaise, hyperventilation, unusual
somnolence. Alcohol potentiates this reaction. Advise patients not
to consume excessive amounts of alcohol.
 Biguanides (cont)
CONTRAINDICATIONS
Renal disease or renal dysfunction (Scr > 1.5 mg/dL in
males, >1.4 mg/dL in females)
Abnormal Scr from any cause including: shock, acute
MI, or septicemia
Metabolic acidosis (including diabetic ketoacidosis
(DKA))
Heart failure requiring pharmacologic therapy; active
liver failure
 Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Sitagliptin (Januvia) 25, 50, 100 mg tablets
Sitagliptin/ (Janumet) 50/500, 50/1000 mg tablets
metformin
Saxagliptin (Onglyza) 2.5, 5 mg tablets
Saxagliptin/ (Kombiglyze 2.5/1000, 5/500, tablets
metformin XR) 5/1000 mg
Indications
Diabetes Mellitus Type II
 
MOA 
Inhibits the breakdown of GLP-1 by DPP-4 therefore increasing GLP-1
levels resulting in increased glucose-dependent insulin release and
decreased level of circulating glucagon and hepatic glucose
production
 DPP-4 (cont)
Patient Info
Hypoglycemia
Weight neutral
Nasopharyngitis/URI
Headache
Onset: Reduction in postprandial serum glucose: 60
minutes
 DPP-4 (cont)
Special Population Considerations:
Renal Impairment: avoid combo drugs w/ metformin
 For sitagliptin:
 CrCl 30-50 mL/min : 50 mg daily
 CrCl < 30 mL/min: 25 mg daily
 End Stage Renal Disease Requiring dialysis: 25 mg daily

Cautions/Severe Adverse Reactions

Acute pancreatitis
Rash (Stevens-Johnson syndrome)
 Sulfonylureas
Glimepiride (Amaryl) 1, 2, 4 mg tablets
Glipizide (Glucotrol, (2.5), 5, 10 mg tablets
Glucotrol XL) (XL)
Glyburide (DiaBeta) 1.25, 2.5, 5 mg tablets

Indications
 
Adjuncts to diet and exercise to lower blood glucose in patients w/ type II
diabetes mellitus
 
MOA

Stimulating insulin release from beta-cells of pancreatic islets

 Sulfonylureas (cont)
Patient Info
Hypoglycemia
GI upset/abdominal pain
Dizziness
Weight gain
Heartburn/epigastric fullness
Onset: glucose lowering effect: 30 minutes with peak at 1.5-3 hours
lasting 24 hours
 Sulfonylureas (cont)
Caution/Severe Adverse Reactions
Syndrome of Inappropriate Anti-diuretic Hormone (SIADH)

CONTRAINDICATIONS
Diabetes complicated by ketoacidosis
Type I DM
Diabetes w/ pregnancy. Pregnancy Cat: C (except glyburide: B)
 Thiazolidinediones (TZD)
Pioglitazone (Actos) 15, 30, 45 mg tablets
Rosiglitazone (Avandia) 2, 4, 8 mg tablets

Indications
As adjunct to diet and exercise for type II diabetes
 
MOA
Increase insulin sensitivity by affecting PPAR-γ (peroxisome
proliferators-activated receptor) at adipose tissue, skeletal muscle and in
the liver.

Special Alert February 2011: Addition of Risk Evaluation and Mitigation

Strategy to rosiglitazone. The medication is restricted to those patients
already on rosiglitazone for fails pioglitazone or cannot be managed by
other oral antidiabetic medications.
 TZD (cont)
Patient Info
Weight gain
Edema
Hypoglycemia esp. when used with other antidiabetic
medications and insulin (not w/ metformin)
May cause or exacerbate heart failure with risk of fluid retention
URI, sinusitis, pharyngitis
Myalgia
Headache
TZD (cont)
Cautions/Severe Adverse Reactions
Black Box: Heart Failure (for all
thiazolidinediones, mainly due to rosiglitazone)
Hepatic failure
Anemia
Bone loss
Ovulation in premenopausal women
Pregancy Cat: C
TZD (cont)
Special Populations Considerations:
Congestive Heart Failure: should be initiated at lowest
approved dose with longer intervals between dose
increases for NYHA class II. Use is not recommended in
patients with NYHA Class III or IV CHF
CONTRAINDICATIONS
NYHA Class III-IV heart failure
Active liver disease (ALT > 2.5 upper limit of
normal)
Insulin
Indications
Type I diabetes mellitus, type II diabetes mellitus, hyperkalemia,
DKA/diabetic coma

MOA
Stimulating peripheral glucose uptake and inhibiting hepatic
glucose production

Patient Info 
Hypoglycemia (BG < 70 mg/dL) esp with higher doses
 Anxiety, blurred vision, palpitations, shakiness, slurred
speech, sweating
Weight gain
Insulin (cont)
Dosing:
Starting daily dose: 0.5-1 unit/kg/day in divided doses
Adjust according to fasting (premeal) blood glucose of 80-130
mg/dL and peak postprandial blood glucose < 180 mg/dL
Provide 50% as long acting insulin and 50% as prandial
insulin
1 unit of can account for 30 grams of carbohydrate (14-50)
1 unit can lower 50 mg/dL blood glucose (10-100)
Insulin Administration

Pharmacology for Technicians by Ballington, Lauglin. EMC Paradigm 2006, Fig. 14.9
Insulin (cont)
Cautions/Severe Adverse Reactions
Severe hypoglycemia (seizure/coma) (BG < 40 mg/dL)
Edema
Lipoatrophy or lipohypertropy at injection site
CONTRAINDICATIONS
Severe hypoglycemia
Allergy or sensitivity to any ingredient of the product
Adjunctive Therapy in Diabetes
Mellitus Type II
 Hypoglycemia
 Complication of treatment!
 Make sure patients inform the people around them of these
symptoms and what to do!
 Symptoms: Anxiety, blurred vision, palpitations,
shakiness, slurred speech, sweating
 Treatment: glucose/simple sugars
 Treatment: glucagon injection
 Dose: 1 mg IM, IV, SQ; may repeat in 20 minutes if
needed
 Adjunctive Therapy (cont)
Energy balance, diet, exercise
 Low-carb, low-fat, calorie-restricted diet is recommended

Cardiovascular disease/Hypertension
 Systolic blood pressure goal < 130 mm Hg
 Angiotensin Converting Enzyme II Inhibitor (ACE-I) is first line
 Renal protective
 Angiotensin Receptor Blockers (ARB) can be used if patient
fails or is intolerant to ACE-I
Adjunctive Therapies (cont)
Dislipidemia
 Patients with type II diabetes have an LDL goal < 100
mg/dL
 Weight loss
 Fiber, omega-3 fatty acids (fish oils) can be used as
adjunct therapy
Adjunctive Therapies (cont)
 Smoking cessation
 Regular Screening for Cardiovascular Diseases and
Coronary Artery Disease
 Depression/Stress/Anxiety/Other psychosocial conditions
need to be screen for regularly
 Diabetic neuropathies especially in extremities need to be
screened for on a regular basis
 Fastidious foot care
 Regular foot exams (annually)
 Eye exams
 Monitor kidney function