Acarbose — Alpha-glucosidase inhibitor (AGI) — FDA-approved antidiabetic agent with ITP-confirmed longevity activity
Acarbose is a pseudo-tetrasaccharide that competitively inhibits intestinal alpha-glucosidases (maltase, sucrase, glucoamylase, glucan-1,4-alpha-glucosidase) and pancreatic alpha-amylase. This delays and reduces the breakdown and absorption of dietary complex carbohydrates, blunting postprandial glucose spikes without increasing insulin secretion. Longevity mechanisms: (1) NIA Interventions Testing Program (ITP) — one of the most reproducible mouse longevity interventions: significant lifespan extension in male mice (+22% median lifespan in males, +5% in females in 3 independent sites); female benefit attenuated because mice consume more food due to acarbose's caloric restriction-like intestinal effect; (2) Caloric restriction mimetic mechanism — by reducing postprandial glucose, acarbose reduces AGE formation, insulin/IGF-1 signaling, and activates AMPK; (3) Gut microbiome modulation — increases production of short-chain fatty acids (propionate, butyrate) via fermentation of unabsorbed carbohydrates; (4) Reduces postprandial insulin spikes, which may extend AMPK activation periods between meals.
Overview
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Compound Class
Alpha-glucosidase inhibitor (AGI) — FDA-approved antidiabetic agent with ITP-confirmed longevity activity
Mechanism of Action
Acarbose is a pseudo-tetrasaccharide that competitively inhibits intestinal alpha-glucosidases (maltase, sucrase, glucoamylase, glucan-1,4-alpha-glucosidase) and pancreatic alpha-amylase. This delays and reduces the breakdown and absorption of dietary complex carbohydrates, blunting postprandial glucose spikes without increasing insulin secretion. Longevity mechanisms: (1) NIA Interventions Testing Program (ITP) — one of the most reproducible mouse longevity interventions: significant lifespan extension in male mice (+22% median lifespan in males, +5% in females in 3 independent sites); female benefit attenuated because mice consume more food due to acarbose's caloric restriction-like intestinal effect; (2) Caloric restriction mimetic mechanism — by reducing postprandial glucose, acarbose reduces AGE formation, insulin/IGF-1 signaling, and activates AMPK; (3) Gut microbiome modulation — increases production of short-chain fatty acids (propionate, butyrate) via fermentation of unabsorbed carbohydrates; (4) Reduces postprandial insulin spikes, which may extend AMPK activation periods between meals.
Regulatory Status
FDA APPROVED for Type 2 Diabetes (adjunct to diet and exercise). All longevity use is OFF-LABEL. Generic drug; very inexpensive.
Evidence Level
B — FDA-approved T2D drug with RCT data (STOP-NIDDM trial, n=1,429: prevented T2D progression in 25% of cases and reduced MI by 35%). ITP lifespan studies: 3 independent sites confirmed +22% male median lifespan extension at 1000 ppm in chow (Harrison et al., 2014, 2019). No completed human longevity RCT.