Acarbose

Acarbose is an oral alpha-glucosidase inhibitor taken with the first bite of each main meal. It lowers post-meal glucose and HbA1c by about 0.5 to 0.8%, does not cause hypoglycaemia alone, is weight neutral, and is almost unabsorbed. Flatulence limits tolerance. It is inexpensive and suits diets rich in starch.

Classification. Alpha-glucosidase inhibitor; a pseudotetrasaccharide. Tablets 25, 50 and 100 mg.

Mechanism. Competitively inhibits alpha-glucosidase and pancreatic alpha-amylase in the small intestine brush border, delaying breakdown of complex carbohydrates and starch to glucose, so glucose absorption extends along the bowel.

Pharmacodynamics. Lowers the post-meal glucose peak and insulin peak. It does not slow absorption of glucose itself, so treat hypoglycaemia with pure glucose and not with sucrose.

Pharmacokinetics. Less than 2% of the active drug is absorbed. Digested by gut bacteria, with about 35% of metabolites absorbed. Unabsorbed drug is excreted in faeces; about 1.5% appears in urine. Half-life about 2 hours, with systemic exposure rising in severe kidney impairment.

Type 2 diabetes, adults.

• Start 25 mg orally once daily with the first bite of the main meal, to limit gastrointestinal effects; increase to 25 mg three times daily with the first bite of each main meal.
• Titrate every 4 to 8 weeks to 50 mg three times daily, and to a maximum of 100 mg three times daily if needed and tolerated.
• Weight 60 kg or less: maximum 50 mg three times daily in some labels.
• No loading dose. Skip the dose when a meal is skipped.

Combination use. Adds to metformin, sulphonylureas, pioglitazone and insulin. Reduce the sulphonylurea or insulin dose if hypoglycaemia occurs. Avoid with intestinal adsorbents.

Adjustments.

• Kidney: no change when eGFR is 25 mL/min/1.73 m2 or more; avoid when under 25.
• Liver: monitor transaminases at higher doses; avoid in cirrhosis.
• Older adults: no change.
• Weight: maximum 50 mg three times daily at 60 kg or less in some labels.
• Children: not licensed.

Contraindications. Inflammatory bowel disease; colonic ulceration; partial intestinal obstruction or predisposition to obstruction; chronic intestinal disorders with marked disorders of digestion or absorption; conditions made worse by gas formation (large hernias); severe renal impairment (eGFR under 25); cirrhosis in some labels; hypersensitivity.

Common adverse effects. Flatulence (up to 70% early), abdominal distension, diarrhoea, abdominal pain; these fade over weeks in many patients and are reduced by slow titration.

Serious adverse effects.

• Raised transaminases at high doses, reversible on stopping; rare hepatitis.
• Intestinal obstruction in predisposed patients; pneumatosis cystoides intestinalis, rarely.
• Hypoglycaemia in combination with sulphonylureas or insulin: only glucose (dextrose) corrects it reliably, since sucrose breakdown is delayed.
• Rare skin reactions and oedema.

Major interactions.

• Digoxin levels fall; monitor.
• Cholestyramine, charcoal and other intestinal adsorbents, and amylase or pancreatin preparations, reduce effect.
• Neomycin increases gastrointestinal effects and post-meal glucose reduction.
• Sulphonylureas and insulin: hypoglycaemia.

Special groups.

• Pregnancy: avoid; use insulin.
• Breastfeeding: avoid.
• Children: not licensed.
• Older adults: flatulence and bowel disease limit use.
• Kidney and liver impairment: avoid if eGFR is under 25; transaminase monitoring at higher doses.
• East Africa: low cost and no hypoglycaemia make it attractive where staples are starch rich (maize, rice, cassava); flatulence and cultural acceptability affect adherence. Rising doses slowly improves tolerance.

Administration. Take with the first bite of the main meal. Chew with the first mouthful or swallow with a little water. The dose has no effect if taken after the meal.

Baseline. HbA1c, eGFR, ALT, history of bowel disease, hernia or obstruction.

Monitoring.

• HbA1c at 3 and 6 months, then every 6 months.
• Post-meal capillary glucose during titration.
• ALT every 3 months in the first year at 100 mg three times daily, then periodically.
• eGFR at least annually.

Stopping thresholds. Stop with intestinal obstruction, persistent severe abdominal symptoms, ALT more than 3 times the upper limit of normal, or HbA1c reduction under 0.5% after 6 months at the maximum tolerated dose.

Referral and escalation. Admit suspected obstruction or severe abdominal pain. Refer hepatitis to hepatology.