Alpha Glucosidase Inhibitors

Alpha glucosidase inhibitors (acarbose, miglitol, voglibose) are oral agents that slow carbohydrate digestion and reduce the postprandial glucose rise. They lower HbA1c by 0.5 to 0.8%, are weight neutral and do not cause hypoglycaemia when used alone.

Mechanism. They competitively and reversibly inhibit brush border alpha glucosidase enzymes in the small bowel, delaying breakdown of starch and disaccharides. Carbohydrate is absorbed more distally, and GLP-1 release rises.

Pharmacokinetics. Acarbose is poorly absorbed (1 to 2% as the parent drug) and acts locally. Miglitol is absorbed but acts in the gut and is cleared by the kidney. They must be taken with the first bite of a meal.

Acarbose. 25 mg once daily with the first bite of the main meal, increased over weeks to 50 mg three times daily, maximum 100 mg three times daily (50 mg three times daily in patients under 60 kg).

Miglitol. 25 mg three times daily, increased to 50 mg, maximum 100 mg three times daily.

Voglibose. 0.2 mg three times daily before meals, in some Asian markets.

Versus other oral agents. Useful with a high-starch diet. Efficacy is lower than metformin and gastrointestinal effects limit use.

• Postprandial hyperglycaemia: an add-on when post-meal glucose is high and HbA1c is near target.
• Diet-based indication: where the diet is rich in rice, maize meal or other starch, which is common in East Africa.
• Prediabetes: reduces progression to diabetes, though gastrointestinal effects reduce adherence.
• Combination with a sulphonylurea or insulin: treat any resulting hypoglycaemia with oral glucose (dextrose), because sucrose is not digested effectively.
• Titration: slow, over 4 to 8 weeks, to reduce flatulence.

Special groups. Pregnancy: avoid. Breastfeeding: avoid. Children: not licensed. Older adults: tolerated, but bloating limits use. Kidney impairment: avoid acarbose at creatinine clearance under 25 mL/min and miglitol under 25 mL/min. Liver impairment: avoid in cirrhosis.

Adverse effects. Flatulence, abdominal distension and diarrhoea in 30 to 70%, rare raised liver enzymes at high doses, and rarely intestinal pneumatosis.

Contraindications. Inflammatory bowel disease, colonic ulceration, partial bowel obstruction, chronic malabsorption, large hernias, cirrhosis and severe renal impairment.

Interactions. Reduces digoxin levels. Charcoal and digestive enzyme preparations reduce effect. Hypoglycaemia with insulin or a sulphonylurea.

Monitoring. Postprandial glucose, HbA1c every 3 months, liver enzymes every 3 months in the first year at doses over 100 mg three times daily, and bowel symptoms.

Referral and escalation. Persistent diarrhoea, abdominal pain with distension, or jaundice.