Acarbose

Human trials: blood glucose

• In a 2005 Cochrane review of 41 randomized trials with 8,130 participants, 30 of them testing acarbose and most lasting about 24 weeks, acarbose lowered HbA1c by 0.8 percentage points, post-load glucose by 2.3 mmol/L and fasting glucose by 1.1 mmol/L compared with placebo, with no clinically relevant effect on blood lipids or body weight. The review found no additional HbA1c effect above 50 mg three times a day, only more side effects, and too few data to judge effects on death or disease (PMID: 15846673).
• In MARCH (2014), a 48-week open-label non-inferiority trial in 788 Chinese adults with newly diagnosed type 2 diabetes, HbA1c fell by 1.11 percentage points with acarbose and 1.12 with metformin, which met the trial's non-inferiority margin; serious adverse events occurred in 2 percent of each group. Bayer Healthcare (China) and a second drug company funded the trial (PMID: 24622668). BodyHackGuide's metformin guide covers the comparison drug.

Human trials: diabetes prevention and heart outcomes

• In STOP-NIDDM (2002), a randomized placebo-controlled trial in 1,429 people with impaired glucose tolerance, participants took acarbose 100 mg or placebo three times a day, and the primary endpoint was diabetes on a yearly glucose tolerance test. Diabetes developed in 32 percent on acarbose and 42 percent on placebo (relative hazard 0.75, 95% CI 0.63 to 0.90, p=0.0015), more people returned to normal glucose tolerance with acarbose, and 31 percent on acarbose against 19 percent on placebo stopped treatment early (PMID: 12086760).
• A 2003 report on cardiovascular events in the same STOP-NIDDM trial, run in nine countries with a mean follow-up of 3.3 years, reported a hazard ratio of 0.51 (95% CI 0.28 to 0.95) for any cardiovascular event with acarbose, a 2.5 percent absolute reduction, and 34 percent fewer new cases of hypertension (PMID: 12876091).
• In ACE (2017), a phase 4 randomized double-blind placebo-controlled trial in 6,522 Chinese patients with coronary heart disease and impaired glucose tolerance followed for a median of 5.0 years, participants took acarbose 50 mg or placebo three times a day. The primary five-point cardiovascular composite occurred in 14 percent on acarbose and 15 percent on placebo (hazard ratio 0.98, 95% CI 0.86 to 1.11, p=0.73), so the primary endpoint was not met, while diabetes developed less often with acarbose (13 against 16 percent, rate ratio 0.82, p=0.005). Bayer AG funded the trial (PMID: 28917545).
• A 2018 Cochrane review included 10 trials of at least one year with 11,814 people at increased risk of diabetes, eight of them testing acarbose. In 3 placebo-controlled acarbose trials with 8,008 participants, new diabetes developed in 16.7 percent on acarbose and 20.3 percent on placebo (risk ratio 0.82, moderate-certainty evidence), and one trial in people with coronary heart disease contributed 64 percent of cases. Acarbose did not clearly change death from any cause (risk ratio 0.98, very low certainty), and the reviewers found no firm evidence of an effect on cardiovascular death or events (PMID: 30592787).

Studies in older adults without diabetes

Two small phase 2 studies of acarbose in older adults without diabetes are registered at ClinicalTrials.gov. A single-arm study at UT Health San Antonio in people aged 70 to 95 enrolled 8, and its posted results report only zeros for its microbiome outcome and cite budgetary restraints (ClinicalTrials.gov NCT02865499). A placebo-controlled crossover study at Montefiore Medical Center in men over 60 with impaired fasting glucose or impaired glucose tolerance was terminated for lack of funding after 28 enrolled, and posted no outcome data (ClinicalTrials.gov NCT02953093). No publication from either study was found in a PubMed search.

Interventions Testing Program lifespan studies (animal data)

• In the 2009 cohort, published in 2014, acarbose at 1,000 ppm in food from 4 months of age increased median lifespan by 22 percent in males (P<0.0001) and 5 percent in females (P=0.01), and age at the 90th percentile of survival by 11 percent in males and 9 percent in females. The male gain was 21 percent at The Jackson Laboratory, 8 percent at Michigan (P=0.054) and 39 percent at UT Health San Antonio (PMID: 24245565).
• In the 2012 cohort, published in 2016, acarbose at 1,000 ppm started at 16 months of age increased male median lifespan by 6 percent and male 90th percentile age by 12 percent (P=0.0001); in females the 2 percent median gain was not significant (P=0.07), while 90th percentile age rose 6 percent (P=0.01) (PMID: 27312235). In the same report, metformin alone at 0.1 percent of the diet did not significantly extend lifespan (PMID: 27312235).
• In the 2013 cohort, published in 2019, acarbose at 400, 1,000 or 2,500 ppm from 8 months of age increased male median lifespan by 11, 17 and 16 percent (each P<0.0001) and female median lifespan by 0, 5 and 4 percent; by log-rank test each dose had a significant effect in both sexes, and the doses did not differ from one another. Male 90th percentile age rose 8 to 11 percent at each dose, female 90th percentile age rose significantly, by 3 percent, only at 1,000 ppm, and food assays found an average of 231 ppm acarbose in diet meant to contain 1,000 ppm (PMID: 30688027). In separate groups of mice in the same report, acarbose at 1,000 ppm from 4 months of age halved the lung tumors seen in 37 percent of male controls examined at 22 to 24 months of age and reduced liver degeneration, significantly only in males, and acarbose at 1,000 ppm from 8 to 22 months of age improved rotarod performance in females but not males (PMID: 30688027).
• In the 2017 cohort, published in 2022, rapamycin at 14.7 ppm plus acarbose at 1,000 ppm from 9 months of age increased median lifespan by 28 percent in females and by more than a third in males, the only treatment in that cohort to increase survival in both sexes at all three sites; started at 16 months, the combination increased median lifespan by 12 percent in females and 14 percent in males (PMID: 36179270). Control mice at UT Health San Antonio lived unusually short lives in that cohort, and in the authors' analysis of the other two sites alone, the 9-month start raised median lifespan by 22 percent in females and 29 percent in males, while the 16-month start left male median lifespan unchanged (PMID: 36179270). The authors judged the male gain larger than in two earlier cohorts given rapamycin alone, a comparison with historical rather than simultaneous controls (PMID: 36179270). BodyHackGuide's rapamycin guide covers that drug.

Healthspan and disease models (animal data)

• In genetically heterogeneous mice, acarbose prevented age-related loss of body mass and improved rotarod balance, rotarod endurance and grip strength in both sexes, and reduced the age-related heart enlargement seen in males (PMID: 32990683). Rotarod and endurance gains were largely similar whether acarbose started at 4 or 16 months of age (PMID: 36342748).
• In Apc(+/Min) mice, a cancer-prone mouse strain that develops intestinal polyps, acarbose at two doses improved median survival; only the higher dose reduced tumor numbers (PMID: 31903726).
• In Ndufs4 knockout mice, a model of the mitochondrial disease Leigh syndrome, acarbose suppressed disease signs and improved survival, and acarbose and rapamycin together had additive effects on the delay of neurological symptoms and on maximum lifespan (PMID: 37365290).

In the STOP-NIDDM trial, 31 percent of people on acarbose and 19 percent on placebo stopped treatment early, and flatulence and diarrhea were the most frequent side effects (PMID: 12086760). In the ACE trial, gastrointestinal disorders were the most common adverse events leading to stopping or changing the study drug, in 7 percent on acarbose and 5 percent on placebo (PMID: 28917545). A 2018 Cochrane review of two prevention trials found non-serious adverse events, mainly gastrointestinal, in 96.9 percent of people on acarbose and 93.3 percent on placebo (PMID: 30592787).

Liver enzymes and hepatitis

In US studies of up to 12 months that included doses up to 300 mg three times a day, rises in the liver enzymes AST or ALT above 3 times the upper limit of normal occurred in 3 percent of people on acarbose and 1 percent on placebo; the rises were asymptomatic, reversible, more common in women and dose related, and in US studies with doses up to 100 mg three times a day, rises at any level were similar with acarbose and placebo (US prescribing information for Precose). The label lists 62 international postmarketing cases of transaminases above 500 IU/L, 29 of them with jaundice, in about 3 million patient-years, and reports cases of fulminant hepatitis with fatal outcome whose relationship to acarbose is unclear (US prescribing information for Precose). A 2006 case report described a 57-year-old woman with type 2 diabetes whose ALT reached 640 U/L on acarbose and returned to normal after acarbose was stopped, a reaction the authors rated as probable (PMID: 16317107).

Other label warnings

The label states that acarbose given alone should not cause hypoglycemia, but acarbose added to a sulfonylurea or insulin can lower blood glucose further, and very rare cases of hypoglycemic shock have been reported with these combinations (US prescribing information for Precose). The label also lists rare postmarketing reports of pneumatosis cystoides intestinalis, gas-filled cysts in the bowel wall, with complications that can include bleeding, intestinal obstruction and perforation, and reports of ileus, skin hypersensitivity reactions, edema and low platelet counts (US prescribing information for Precose). Small falls in hematocrit were more common with acarbose than with placebo (US prescribing information for Precose).

Animal toxicology

In a 104-week study and its repeat, Sprague-Dawley rats fed very high doses of acarbose had more kidney tumors and benign Leydig cell tumors; the rise in kidney tumors did not recur when carbohydrate deprivation was prevented with added glucose or when acarbose was given by gavage after meals, no increase in kidney tumors was found in Wistar rats, and two hamster studies showed no evidence of carcinogenicity (US prescribing information for Precose). In the Interventions Testing Program, acarbose lowered body weight in mice, more in females than in males (PMID: 24245565).