Overview of Oral Hypoglycemics

and their Correct Use

Dr. Sunishka Ponnamperuma
Senior Registrar in Medicine
 Types of Oral Hypoglycemics
1. Biguanides
Metformin
2. Sulphonylureas
Glibenclamide, Tolbutamide, Gliclazide, Glimepiride
3. Thiazolidinediones (Glitazones)
Pioglitazone, Rosiglitazone
4. α - Glucosidase Inhibitors
Acarbose
5. Meglitinides
Repaglinide
6. DPP4 inhibitors (Gliptins)
Sitagliptin, Vildagliptins
Sulphonylureas Alpha Glucosidase Inhibitors
( Glibenclamide, Tolbutamide) (Acarbose)
Meglitinide
Gliptins

Biguanides (Metformin)

Glitazones (Pioglitazone)
 Biguanides (Metformin)
• Mechanism of Action
– Increase peripheral utilization of glucose
– Inhibits gluconeogenesis
– Impaired glucose absorption from gut

• Indications
– Type 2 diabetes
• (Especially BMI > 22)
 Biguanides (Metformin)
• Dosage
– Max 2550 mg/day ( 3 divided doses)
– Initiated 500 mg bd
– Increased 500 mg every week

• Significant side effects

– Gastrointestinal:
• Diarrhea (10% to 53%), nausea/vomiting (7% to 26%), flatulence
(12%)
– Neuromuscular & skeletal:
• Weakness (9%)
 Biguanides (Metformin)
• Contraindications
– hypersensitivity to metformin
– renal disease or renal dysfunction (serum creatinine ≥1.5
mg/dL in males or ≥1.4 mg/dL in females)
– acute or chronic metabolic acidosis with or without
coma (including diabetic ketoacidosis)
• Avoid
– Liver disease (not NASH)
– Acute heart failure
– Alcoholism
 Sulphonylurea
• Drugs
– 1st Generation
• Tolbutamide
– 2nd Generation
• Glibenclamide, Gliclazide, Glimepiride

• Mechanism of action
– Release of insulin from β-cells
– Reduction of serum glucagon concentration
– Potentiation of insulin action on target tissues
 Sulphonylurea
• Significant side effects
– Nausea, vomiting, abdominal pain, diarrhea
– Hypoglycaemia
– Weight gain

• Contraindications
– Type 1 DM ( insulin dependent)

• Avoid
– Pregnancy, lactation
– Parenchymal disease of the liver or kidney
– Major stress
 Sulphonylurea
• Dosage
– Tolbutamide 250mg bd to 1000mg tds
– Glibenclemide 2.5mg bd to 10mg bd
– Glipizide 2.5mg bd to 10mg bd
– Gliclazide 40 mg bd to 160mg bd
• 15-30 minutes before meals
 Sulphonylurea
• Duration of biologic effect (hours)
– Tolbutamide 14-16
– Glibenclemide 20-24+
– Glipizide 14-16
– Gliclazide 24
 Thiazolidinediones
• Drugs & Dosage
– Pioglitazone 15 mg to 45 mg/day (daily/divided)
– Rosiglitazone 4mg to 8mg/day (daily/divided)

• Mechanism of action
– Increase target tissue sensitivity to insulin by:
• reducing hepatic glucose output & increase glucose uptake &
oxidation in muscles & adipose tissues
– They do not cause hypoglycemia (similar to metformin
and acarbose )
 Thiazolidinediones
• Significant side effects
– Mild to moderate edema
– Heart failure
– Weight gain
– Myocardial ischemia
– Headache
– Myalgia
– Hepatotoxicity
– Increase in cholesterol (incl. HDL)
 Summary Oral Hypoglycemics
• Many classes of drugs used, mainly
– Biguanides (Metformin)
– Sulphonylureas (Glibenclamide, Tolbutamide)
• Should be taken 15-30 minutes before meals
• Many side effects, which defers from group
– Metformin (GI)
– Sulphonylurea (hypoglycemia, weight gain)
• Sulphonylureas drug show similar efficacy but the
pharmacokinetics and side effects differ
Thank you