Miglitol

Miglitol 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 0.7%, does not cause hypoglycaemia alone and is weight neutral. Unlike acarbose it is absorbed and excreted by the kidney. Availability is limited in many markets.

Classification. Alpha-glucosidase inhibitor; a 1-deoxynojirimycin derivative. Tablets 25, 50 and 100 mg.

Mechanism. Reversibly inhibits brush border alpha-glucosidases in the small intestine, delaying digestion of complex carbohydrates and sucrose to glucose. It has no effect on pancreatic alpha-amylase.

Pharmacodynamics. Lowers the post-meal glucose and insulin peaks. Hypoglycaemia from combination therapy must be treated with pure glucose, not sucrose.

Pharmacokinetics. Almost completely absorbed at 25 mg; absorption falls at higher doses, to about 50 to 70% at 100 mg. Not protein bound and not metabolised. Excreted unchanged in urine. Half-life about 2 hours; exposure rises in renal impairment.

Type 2 diabetes, adults.

• Start 25 mg orally three times daily with the first bite of each main meal; where flatulence is a problem, begin once daily and step up.
• After 4 to 8 weeks increase to 50 mg three times daily; maximum 100 mg three times daily.
• No loading dose. Skip the dose when a meal is skipped.

Combination use. Adds to metformin, sulphonylureas and insulin. Reduce the sulphonylurea or insulin dose if hypoglycaemia occurs.

Adjustments.

• Kidney: avoid when eGFR is under 25 mL/min/1.73 m2; with eGFR 25 to 59 monitor closely as the drug accumulates.
• Liver: no change.
• Older adults: no change.
• Weight: no weight-based dosing.
• Children: not licensed.

Contraindications. Inflammatory bowel disease; colonic ulceration; partial intestinal obstruction or predisposition to it; chronic intestinal disorders with marked digestion or absorption problems; severe renal impairment (eGFR under 25); diabetic ketoacidosis; hypersensitivity.

Common adverse effects. Flatulence, diarrhoea, abdominal pain, abdominal distension; reduced by slow titration and often fading over weeks. Low serum iron without anaemia reported.

Serious adverse effects.

• Hypoglycaemia in combination with sulphonylureas or insulin: treat with glucose, not sucrose.
• Intestinal obstruction in predisposed patients.
• Rare skin rash.

Major interactions.

• Propranolol and ranitidine: reduced miglitol exposure.
• Digoxin levels fall; monitor.
• Intestinal adsorbents (charcoal) and digestive enzyme preparations reduce effect.
• Sulphonylureas and insulin: hypoglycaemia.

Special groups.

• Pregnancy: avoid; use insulin.
• Breastfeeding: avoid; excreted in milk in small amounts.
• Children: not licensed.
• Older adults: flatulence and bowel disease limit use.
• Kidney and liver impairment: avoid if eGFR is under 25; no liver adjustment.
• East Africa: rarely stocked; acarbose is the usual alternative where an alpha-glucosidase inhibitor is wanted.

Administration. Take with the first bite of the main meal; effect is lost if taken after the meal.

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

Monitoring.

• HbA1c at 3 and 6 months, then every 6 months.
• Post-meal capillary glucose during titration.
• eGFR at least annually; every 3 to 6 months when under 60.

Stopping thresholds. Stop with intestinal obstruction, persistent severe abdominal symptoms, eGFR under 25, or HbA1c reduction under 0.5% after 6 months at the maximum tolerated dose.

Referral and escalation. Admit suspected obstruction or severe abdominal pain.