Rapamycin plus acarbose

Rapamycin and acarbose are the two drugs with the most consistently replicated lifespan effects in the NIA Interventions Testing Program, and in 2017 the programme fed them together. This page covers that experiment. Each drug has its own page.

In people there is nothing. No trial, registered or published, has given rapamycin and acarbose together. Searches of ClinicalTrials.gov for the pair return no study. Rapamycin's small human healthspan trials and acarbose's diabetes and cardiovascular trials are described on their own pages; neither drug has human lifespan data alone, and the combination has none at all.

In mice, the 2017 cohort received rapamycin at 14.7 ppm and acarbose at 1,000 ppm in chow, starting either at 9 months (RaAc9) or at 16 months (RaAc16). Started at 9 months, pooled across three sites, female median lifespan rose from 868 to 1,107 days, 28 percent (p < 0.0001), and 90th percentile survival rose 21 percent; male median rose from 718 to 981 days, which the paper's text gives as 34 percent and its pooled table as 37 percent (p < 0.0001), with 90th percentile survival up 24 percent. It was the only treatment in the cohort that significantly extended survival in both sexes at each site analysed separately, though the size varied: 32, 8 and 35 percent in females and 13, 25 and 49 percent in males at the three sites. Started at 16 months, the gains were smaller but significant: median +12 percent in females and +14 percent in males (both p = 0.001), with 90th percentile survival up 15 and 18 percent.

The comparison that matters is against each drug alone, and the cohort had no single-drug arms, so the authors compared against earlier rapamycin-only cohorts given the same dose. Males on rapamycin alone had lived 10 percent longer than controls in the 2006 cohort and 5 percent in the 2009 cohort; RaAc9 males lived 19 percent longer using the two sites common to those cohorts and 29 percent using all three, which the authors read as the combination being more potent than rapamycin alone in males, with the caveat that comparisons across years warrant caution. Females on rapamycin alone had gained 18 percent in both earlier cohorts; RaAc9 females gained 20 percent on the two-site comparison and 27 percent on three sites, which the authors describe as "neither distinctly better nor worse" than rapamycin alone, consistent with acarbose's small effect in females on its own.

Both drugs are approved prescription medicines for other indications. The combination is off-label everywhere.

The NIA Interventions Testing Program runs each compound in parallel at three sites (The Jackson Laboratory, the University of Michigan and UT Health San Antonio) in genetically heterogeneous UM-HET3 mice, tests both sexes, analyses them separately, pools the sites in a site-stratified log-rank test, and publishes every result whether or not the compound worked. It is publicly funded by the National Institute on Aging with no pharmaceutical sponsorship. In the 2017 cohort the rapamycin plus acarbose arm produced the largest pooled lifespan effect the programme has published, 28 percent in females and 34 to 37 percent in males at the median, significant at every site in both sexes, with late survival extended 21 and 24 percent. Started at 16 months it still gave 12 to 14 percent. Those numbers are real and they are mouse numbers.

The limit is the same one that affects the metformin plus rapamycin arm: no contemporaneous single-drug groups. The claim that the combination beats rapamycin alone rests on comparing this cohort's males against rapamycin-only males from cohorts run in 2006 and 2009, which gained 10 and 5 percent; on that comparison the combination looks clearly better in males (19 to 29 percent) and about the same in females (20 to 27 percent against 18). The authors state the caution about cross-year comparisons themselves. A further complication is dose: rapamycin alone at three times this dose gave 23 to 26 percent median gains in an earlier cohort, so part of what acarbose appears to add in males might also be reachable by more rapamycin, and the experiment cannot distinguish those. What it does show without qualification is that a two-drug regimen of approved generics started in midlife extended both median and maximal lifespan in both sexes at three independent sites, which no single ITP compound has done at this magnitude.

No human trial will come from industry, because both drugs are generic. Academic trials of rapamycin alone in older adults are small and recent; nobody has proposed adding acarbose. The absence of a trial is not evidence against the combination, and it leaves any harm from taking two drugs with real side effects for years equally unmeasured.