Alpha-glucosidase inhibitors

Mechanism. Alpha-glucosidase inhibitors are competitive, reversible inhibitors of the α-glucosidase enzymes of the intestinal brush border — glucoamylase, sucrase, maltase and isomaltase — and acarbose additionally inhibits pancreatic α-amylase. They delay the breakdown of complex carbohydrates and disaccharides into absorbable monosaccharides, so glucose absorption is slowed and shifted distally along the small intestine. The result is a blunted postprandial glucose peak. They do not stimulate insulin secretion and do not cause hypoglycaemia when used alone.

Drugs and dosing. Acarbose 25–100 mg three times daily, miglitol 25–100 mg three times daily, and voglibose 0.2–0.3 mg three times daily — voglibose being widely used in India. Each must be taken with the first mouthful of each main meal; a dose taken without food has no effect. Start low (acarbose 25 mg once daily) and titrate over weeks to limit flatulence, which is the main reason for discontinuation.

Indications and place in therapy. Type 2 diabetes with predominantly postprandial hyperglycaemia, as monotherapy or as add-on to metformin, sulphonylureas or insulin. The expected HbA1c reduction is modest — about 0.5–0.8% — so they are second- or third-line agents. They are particularly relevant in India, where high-carbohydrate diets of rice, wheat and millets produce a large postprandial excursion, and where the drugs are cheap. They are also weight-neutral or mildly weight-reducing, and they were shown to reduce progression from impaired glucose tolerance to diabetes.

Advantages in the older patient. No intrinsic hypoglycaemia — the single most valuable property in geriatric practice; no weight gain; no systemic absorption to speak of (acarbose is minimally absorbed), so few systemic drug interactions; and a lowering of postprandial glucose, which is the component that contributes relatively more to total hyperglycaemia in older people than basal glucose does.

Adverse effects, precautions and one critical rule. Adverse effects are almost entirely gastrointestinal and arise from colonic bacterial fermentation of unabsorbed carbohydrate: flatulence, abdominal distension, borborygmi, cramps and diarrhoea — poorly tolerated and often socially unacceptable in older adults. Raised transaminases occur with higher acarbose doses, so monitor liver function. Contraindications: inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to it, chronic intestinal disease with malabsorption, large hernias, cirrhosis, and severe renal impairment (avoid acarbose if eGFR is below 25–30). The critical rule: if hypoglycaemia occurs because the patient is also on a sulphonylurea or insulin, it must be treated with oral glucose (dextrose) or intravenous dextrose — NOT with sucrose, table sugar, sweets or fruit juice, because the drug blocks the very enzyme that would split sucrose into absorbable glucose.

Alpha-glucosidase inhibitors have been displaced from international algorithms but retain a defined niche in Indian practice. Current international guidance — ADA Standards of Care 2026 and the ADA/EASD consensus — organises second-line therapy around cardiovascular, renal and weight benefit, and on those criteria the alpha-glucosidase inhibitors have no demonstrated cardiovascular or renal protection and so rank below SGLT2 inhibitors and GLP-1 receptor agonists; the ACE (Acarbose Cardiovascular Evaluation) trial found that acarbose did not reduce major adverse cardiovascular events in patients with impaired glucose tolerance and coronary disease, although it did reduce progression to diabetes. However, RSSDI and Indian national guidance continue to recognise a role for them where postprandial hyperglycaemia predominates on a high-carbohydrate diet, where cost is decisive, and — importantly for geriatrics — where hypoglycaemia must be avoided at all costs, such as in the frail patient living alone. The examinable summary: a safe, cheap, hypoglycaemia-free but weakly effective and poorly tolerated agent, now a third-line option internationally and a legitimate second-line adjunct in the Indian setting.