Alpha-glucosidase Inhibitors and Amylin Analogs

Alpha-glucosidase Inhibitors

• Used for type 2 diabetes mellitus (DM)
• Examples: Acarbose, Miglitol
• Mechanism: Inhibit the enzyme alpha-glucosidase, which breaks down starches and disaccharides into glucose.
• Effect: Delays carbohydrate absorption, reducing post-prandial glucose (PPG) levels.
• PPG reduction: Approximately 40-50 mg/dL.
• Fasting blood glucose (FBG) change: Relatively unchanged
• A1C reduction: Modest, 0.3%–1%.
• Ideal candidates: Patients with near-normal FBG and high PPG levels.
• Side effects: Flatulence, abdominal pain, diarrhea; can be minimized with slow dose titration.
• Contraindications: Cirrhosis, colonic ulcers, intestinal disease/obstruction, inflammatory bowel disease, diabetic ketoacidosis.

Amylin Analogs

• Example: Pramlintide (Symlin)
• Synthetic amylin analog.
• Actions:
  • Reduces glucagon secretion
  • Slows gastric emptying
  • Increases satiety.
• Effect: Lowers PPG levels and A1C.
• A1C reduction:
  • Type 2 DM: ~0.6%
  • Type 1 DM: 0.4%–0.5% (5–6 mmol/mol Hb).
• Use: Primarily adjunctive therapy for type 1 DM, not achieving PPG goals despite mealtime insulin.
• Also useful for weight loss and lower mealtime insulin doses.
• Side effects: Nausea, vomiting, anorexia.
• Hypoglycemia risk: Minimal when used alone; increased risk with insulin.
• Dose reduction (30-50%) of mealtime insulin is recommended when initiating pramlintide.
• Dosing (type 2 DM): Begin with 60 mcg SC before meals, titrate to maximum 120 mcg SC as tolerated and needed based on PPG.
• Dosing (type 1 DM): Begin with 15 mcg SC before meals and titrate up to 60 mcg SC before each meal, if tolerated.

Glucagon-like Peptide 1 Receptor Agonists (GLP1-RAs)

• Mechanism: Incretin hormone (GLP-1) agonists.
• Action:
  • Stimulates insulin secretion.
  • Suppresses glucagon secretion.
  • Decreases hepatic glucose production.
  • Slows gastric emptying, increases satiety, causing weight loss (1–3 kg).
• Types: Dulaglutide, Exenatide, Exenatide XR, Lixisenatide, Liraglutide, Semaglutide
• Short-acting agents (exenatide, lixisenatide): Primarily lower PPG levels.
• Long-acting agents (dulaglutide, liraglutide, exenatide XR, semaglutide): Lower both FPG and PPG, more impact on FPG.
• Side effects: Nausea, vomiting, diarrhea; dose-dependent, usually transient.
• Eating slowly and stopping when satiated can lessen side effects.
• Other adverse effects: Injection site reactions and potential hypersensitivity reactions (including anaphylaxis and angioedema).
• Hypoglycemia risk: Lower risk with metformin or thiazolidinediones (TZDs); increased risk with sulfonylureas or insulin.
• Use: Not typically first-line therapy. Suitable for patients with established cardiovascular disease (atherosclerosis) or chronic kidney disease, hypoglycemia avoidance, weight loss needs.