Acarbose — The Glucose Absorption Inhibitor
Acarbose is an alpha-glucosidase inhibitor that slows the digestion and absorption of dietary carbohydrates, blunting post-meal glucose and insulin spikes. It is one of only three compounds (alongside rapamycin and 17α-estradiol) that have reproducibly extended lifespan in the NIA Interventions Testing Program (ITP) in genetically diverse mice — the gold standard for longevity drug testing.
Mechanism of Action
Acarbose competitively inhibits intestinal alpha-glucosidases (maltase, sucrase, glucoamylase), slowing starch digestion and reducing the glycaemic index of all carbohydrate-containing meals. This reduces post-meal glucose excursions, lowers insulin secretion, and reduces advanced glycation end-product (AGE) formation. In mice, acarbose also shifts the gut microbiome toward butyrate-producing bacteria.
Human Trial Evidence
Approved for type 2 diabetes in 1995. The STOP-NIDDM trial showed acarbose reduced type 2 diabetes incidence by 25% and cardiovascular events by 49% in pre-diabetics. The NIA ITP showed acarbose extended median lifespan in male mice by 22% and female mice by 5% (Harrison et al., Aging Cell, 2014). Human longevity trials are not yet completed.
Dosing Protocol
25–100 mg with each meal (standard diabetes dose). Longevity-focused practitioners use 25–50 mg with carbohydrate-containing meals. Prescription only in most countries. Best taken at the start of a meal. Dose titrated slowly to minimise GI side effects.
Safety & Contraindications
Main side effects: GI (flatulence, bloating, diarrhoea) due to fermentation of undigested carbohydrates in the colon — common, dose-dependent, usually improves over time. Contraindicated in inflammatory bowel disease, cirrhosis, and renal impairment. No hypoglycaemia risk when used alone. Requires prescription.