Anti-Diabetic Drugs

Question 1

Classes of anti-diabetic drugs & examples

Answer 1

Insulins

• Ultra short acting (insulin lispro, insulin aspart, insulin glulisine)
• Short acting (regular insulin)
• Intermediate acting (NPH, insulin detemir)
• Long acting (insulin glargine, insulin detemir)

Oral Hypoglycemic Agents

• Insulin Secretagogues
  1. Sulphonylureas (Glibenclamide, Glipizide)
  2. Prandial Glucose Regulators/Meglitinides (Repaglinide)
  3. Dipeptidyl peptidase-4 Inhibitors (Sitagliptin)
• Insulin Sensitisers
  4. Biguanides (Metformin)
  5. Thiazolidinediones (Rosiglitazone)
• Insulin Release Sparers
  6. α-glucosidase Inhibitors (Acarbose)

Question 2

Toxicity of insulins (4)

Answer 2

1. Hypoglycemia
2. Lipodystrophy - lipoatrophy, lipohypertrophy
3. Factitious hypoglycemia
4. Allergy, redness at injection site

Question 3

Mechanism of action of sulphonylureas

Answer 3

Blocks ATP sensitive K channels - depolarisation - opens voltage gated Ca channels - stimulates insulin release

Question 4

Toxicity of sulphonylureas (5)

Answer 4

1. GIT related
2. Rash
3. Hypoglycemia (esp glibenclamide, long half life)
4. Tolbutamide (1G) - Hypothyroidism, liver damage, nephrotic syndrome, teratogenicity in animals
5. Drug interactions - increases hypoglycemic effects of sulphonylureas
   - Salicylates, NSAIDs - displace sulphonylureas from plasma protein binding sites
   - Sulphonamides - inhibit hepatic metab of sulphonylureas

Question 5

Mechanism of action of meglitinides

Answer 5

Acts on 3 binding sites (overlaps with sulphonylureas) - regulates K+ efflux through ATP-dependent K+ channels - increased Ca influx - more insulin release

Question 6

Toxicity of meglitinides

Answer 6

No major adverse effects
No cross allergy with sulphonylureas
Use with caution in liver/renal impairment

Question 7

Mechanism of action of DPP-4 inhibitors

Answer 7

Inhibits hydrolytic action (breakdown) of DPP-4 on incretins - increases blood levels of GLP-1 & GIP - increases insulin and decreases glucagon levels - normalizes glucose levels

GLP-1 - glucagon-like peptide - promotes insulin release
GIP - gastric inhibitory peptide - reduces release of glucagon from pancreas

Question 8

Toxicity of DPP-4 inhibitors

Answer 8

1. Nasopharyngeal, URTI
2. Headaches
3. Dose reduction req in renal-impaired patients

Lower occurrence of hypoglycemia & weight gain

Question 9

Mechanism of action of biguanides

Answer 9

1. Increases insulin receptor density & sensitivity (main action)
2. Directly stimulates glycolysis in peripheral tissues
3. Reduces hepatic gluconeogenesis
4. Decreases glucose absorption from GIT
5. Reduces glucagon release

Question 10

Uses of biguanides

Answer 10

1. Obesity related type 2 DM - reduces TG levels & promotes weight loss

Question 11

Toxicity of biguanides (4)

Answer 11

1. GIT related
2. Metallic taste
3. Weight loss
4. Lactic Acidosis - inhibits lactate conversion to glucose

Question 12

Mechanism of action of thiazolidinediones

Answer 12

Activates PPAR-

Question 13

Toxicity of thiazolidinediones (5)

Answer 13

1. Water retention
2. Weight gain (not used in obesity related type 2 DM)
3. Increased HDL levels
4. Induced ovulation
5. Hepatic impairment

Question 14

Mechanism of action of α-glucosidase inhibitors

Answer 14

Does not depend on insulin for its effects

- Competitively inhibits intestinal glucosidases - decreased digestion of carbohydrates & decreased glucose production

Question 15

Uses of α-glucosidase inhibitors

Answer 15

Blunts rise in post-prandial blood glucose

• Does not work on lactose!! lactase still functions - decrease milk intake
• Use in combination with sulphonylureas/insulin to improve glucose control

Question 16

Toxicity of α-glucosidase inhibitors (3)

Answer 16

1. Flatulence
2. Diarrhea
3. Hepatitis (high doses)