Acarbose

Acarbose is a complex oligosaccharide that competitively inhibits intestinal alpha-glucosidase enzymes. It targets postprandial (after-meal) glucose excursions and represents a unique mechanism in type 2 diabetes management.

Mechanism of Action

Acarbose reversibly inhibits alpha-glucosidase enzymes in the small intestine brush border. Its inhibitory potency follows this rank order: glucoamylase > sucrase > maltase > isomaltase. These enzymes break down complex carbohydrates into simple sugars; their inhibition slows the digestion of complex carbohydrates and delays glucose absorption.

• Reduces postprandial hyperglycemia by flattening glucose peaks after meals.
• Does not stimulate insulin secretion and therefore does not cause hypoglycemia when used alone.
• Modestly improves insulin sensitivity and lipid profiles.
• Weight-neutral.

Pharmacokinetics

Acarbose is designed to act locally in the gastrointestinal tract; its systemic exposure is intentionally minimal.

• Bioavailability (parent drug): less than 1–2% of the administered dose is absorbed as intact acarbose. However, approximately 35% of total radioactivity from a radiolabeled dose is absorbed over 96 hours — representing absorbed degradation products and metabolites. Peak radioactivity in plasma occurs at 14–24 hours, reflecting the time for intestinal microbial metabolism and subsequent metabolite absorption.
• Volume of distribution: not applicable (primarily local GI action).
• Protein binding: negligible for parent drug.
• Metabolism: degraded by intestinal bacteria and digestive enzymes (including intestinal glucosidases) into more than 13 metabolites, predominantly methylated, sulfated, and glucuronide conjugates. This metabolic transformation occurs in the gut before absorption.
• Half-life: approximately 2 hours (plasma half-life of the absorbed metabolite fraction).
• Clearance: renal elimination of absorbed metabolites.
• Excretion: approximately 50% of the administered dose is excreted in feces within 96 hours (primarily as unabsorbed parent drug); approximately 34% of dose is renally excreted as metabolites.

The pharmacological effect depends entirely on the presence of carbohydrates in the meal — there is no clinically meaningful effect during fasting. Maximal effect occurs when acarbose is present at the start of digestion.

• HbA1c reduction: 0.5–0.8% from baseline; greater effect in patients with higher baseline HbA1c.
• Postprandial glucose: significant reduction in glucose excursions (30–40 mg/dL).
• Fasting glucose: modest reduction (10–20 mg/dL).
• STOP-NIDDM trial: 49% reduction in progression from impaired glucose tolerance to type 2 diabetes; 49% reduction in cardiovascular events; 34% reduction in new-onset hypertension.
• Weight effects: weight-neutral or modest weight loss.

• Type 2 diabetes mellitus as monotherapy adjunct to diet, or in combination with other oral antidiabetic agents (metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists) or insulin.
• Prediabetes / impaired glucose tolerance (in some regions): prevention of progression to type 2 diabetes.
• Particularly useful in patients with predominantly postprandial glucose elevations.

• Hypersensitivity to acarbose or any of the excipients.
• Chronic intestinal disorders associated with marked disorders of digestion or absorption, inflammatory bowel disease (Crohn’s disease, ulcerative colitis), colonic ulceration, or partial intestinal obstruction (or predisposition to it).
• Conditions that may deteriorate due to increased intestinal gas formation (Roemheld syndrome, large hernias, intestinal stenosis).
• Severe renal impairment (serum creatinine >2 mg/dL or eGFR <25 mL/min).
• Severe hepatic impairment (cirrhosis).
• Diabetic ketoacidosis.
• Pregnancy and breastfeeding.

Use is not recommended in children and adolescents under 18 years due to limited data.

Very Common (>10%) — dose-dependent and resulting from fermentation of undigested carbohydrates in the colon: flatulence (most common, up to 74%), abdominal distension, diarrhea, abdominal pain or discomfort, borborygmi (intestinal rumbling). These typically decrease with continued treatment.

Common (1–10%): nausea, soft stools, increased intestinal gas.

Rare (<0.1%): elevated liver enzymes (transient, usually asymptomatic), hepatitis, jaundice, severe allergic reactions, edema, ileus or subileus in predisposed patients.

Very Rare: thrombocytopenia.

Side effects are most prominent at treatment initiation and with high-carbohydrate meals; they can be minimized by slow dose titration and dietary modification.

• Intestinal adsorbents (e.g., charcoal): avoid concomitant use — reduces acarbose efficacy.
• Digestive enzymes (e.g., amylase, pancreatin): counteract acarbose.
• Digoxin: may reduce digoxin absorption — monitor levels.
• Insulin, sulfonylureas, meglitinides: increased risk of hypoglycemia when combined.

Critical hypoglycemia management note: when acarbose is combined with insulin or insulin secretagogues, hypoglycemia must be treated with glucose (dextrose), not table sugar (sucrose) — acarbose blocks the breakdown of sucrose in the gut. Glucagon injection remains effective. All healthcare providers should be informed about acarbose use.

Acarbose must be taken with the first bite of each main meal to be effective. Taken before or after the meal, efficacy is significantly reduced. Tablets may be swallowed whole with liquid or chewed with the first mouthful of food.

Adults

• Initial dose: 50 mg once daily with the evening meal, or 50 mg twice/three times daily with main meals.
• Titration: increase gradually every 4–8 weeks based on 1-hour postprandial glucose and gastrointestinal tolerability. Typical progression: 50 mg once daily → 50 mg twice daily → 50 mg three times daily → 100 mg three times daily.
• Maintenance: usually 50 mg three times daily.
• Maximum: 100 mg three times daily; for patients under 60 kg, maximum is 50 mg three times daily.

Special Populations

• Elderly: no dose adjustment required, but use lower doses if GI sensitivity is increased.
• Renal impairment: mild–moderate, no adjustment; severe (eGFR <25 mL/min or creatinine >2 mg/dL), contraindicated.
• Hepatic impairment: mild, use with caution and monitor liver function; moderate–severe, contraindicated.

Missed Dose

Take with the next meal. Do not take between meals or at bedtime — acarbose is ineffective without food. Do not double dose.

Liver Function Monitoring

Monitor liver enzymes (ALT, AST) before starting therapy and at 3, 6, and 12 months during the first year, then annually if stable. Monitor more frequently with baseline abnormal liver function or with dose increases. Discontinue if ALT/AST exceeds 3× upper limit of normal or signs of liver dysfunction develop.

Diet and Lifestyle

Maintain consistent carbohydrate intake. Effectiveness depends on dietary carbohydrate content; low-carbohydrate meals result in minimal GI effects but also minimal glucose-lowering effect.

Pregnancy and Breastfeeding

Contraindicated in pregnancy (insulin is preferred for gestational diabetes) and during breastfeeding (transfer to breast milk not established).

Effect on Driving

Does not affect ability to drive or operate machinery on its own. When combined with insulin or sulfonylureas, patients should be aware of hypoglycemia risk.

Store below 25°C in the original package to protect from moisture. Keep in a dry place and out of reach of children.

3 years. Do not use after the expiry date.

Prescription required.