What is the mechanism of action, indications, side effects, and contraindications of Glucobay (Acarbose)?

Glucobay (Acarbose): Mechanism of Action, Indications, Side Effects, and Contraindications

Acarbose is an alpha-glucosidase inhibitor that works by competitively inhibiting intestinal alpha-glucosidases in the small intestine, delaying carbohydrate digestion and absorption, thereby reducing postprandial hyperglycemia in diabetic patients. 1

Mechanism of Action

Acarbose functions through a unique mechanism different from other antidiabetic medications:

• Acts as a competitive, reversible inhibitor of pancreatic alpha-amylase and intestinal alpha-glucosidase enzymes 1
• Inhibits the breakdown of complex carbohydrates into absorbable monosaccharides in the small intestine 1
• Delays glucose absorption rather than completely blocking it, resulting in:
  • Attenuated postprandial blood glucose elevations
  • Reduced insulin secretion
  • Blunted glycemic excursions 2
• Works locally in the gastrointestinal tract with minimal systemic absorption (less than 2% absorbed as active drug) 1

Indications

Acarbose is indicated for:

1. Type 2 diabetes mellitus:

   • First-line therapy in patients inadequately controlled by diet alone 2
   • Add-on therapy to other oral antidiabetic medications (metformin, sulfonylureas, thiazolidinediones) 2
   • Adjunctive therapy to insulin in both Type 1 and Type 2 diabetes 1

2. Dumping syndrome:

   • Management of postprandial hypoglycemia in patients who have undergone gastric surgery 2
   • Reduces early hyperglycemic and hyperinsulinemic responses and subsequent reactive hypoglycemia 2

Side Effects

The most common adverse effects are gastrointestinal in nature:

1. Gastrointestinal effects (most common):

   • Flatulence (74% of patients)
   • Diarrhea (31% of patients)
   • Abdominal pain (19% of patients)
   • Abdominal distension 1, 2

2. Other adverse effects:

   • Elevated liver enzymes (transaminases) 1
   • Small reductions in hematocrit 1
   • Low serum calcium and plasma vitamin B6 levels (may be spurious) 1

3. Rare but serious adverse effects:

   • Fulminant hepatitis with fatal outcome (rare postmarketing reports)
   • Pneumatosis cystoides intestinalis
   • Hypersensitive skin reactions (rash, erythema, urticaria)
   • Thrombocytopenia 1

Important note: The gastrointestinal side effects typically diminish over time with continued use. Starting with a low dose and gradually increasing it can help reduce these effects. 2

Contraindications

Acarbose is contraindicated in patients with:

1. Known hypersensitivity to the drug 1
2. Diabetic ketoacidosis 1
3. Cirrhosis 1
4. Inflammatory bowel disease 1
5. Colonic ulceration 1
6. Partial intestinal obstruction or predisposition to intestinal obstruction 1
7. Chronic intestinal diseases with marked disorders of digestion or absorption 1
8. Conditions that may deteriorate due to increased gas formation in the intestine 1

Dosage and Administration

• Initial dose: Start with 25 mg three times daily with the first bite of each main meal 2
• Gradual titration: Increase slowly to minimize gastrointestinal side effects
• Maximum dose:
  • 50 mg three times daily for patients weighing ≤60 kg
  • 100 mg three times daily for patients weighing >60 kg 2

Special Considerations

1. Hypoglycemia management: When patients using acarbose develop hypoglycemia, they should be treated with glucose or honey, not sucrose (table sugar) or starchy foods, as acarbose inhibits the breakdown of these carbohydrates 2

2. Elderly patients: Plasma concentrations may be approximately 1.5 times higher in elderly patients, though this difference is not statistically significant 1

3. Renal impairment: Patients with severe renal impairment (CrCl <25 mL/min/1.73m²) may have 5 times higher peak plasma concentrations 1

4. Drug interactions: May affect bioavailability of metformin and may be less effective when used with intestinal adsorbents and digestive enzyme preparations 1

Acarbose represents a valuable option in diabetes management with the added benefit of not causing weight gain or hypoglycemia when used alone, making it particularly suitable for obese or elderly patients.