No source used here shows that metformin slows aging or extends life. The evidence offered comes from observational studies, which cannot show cause and effect, from reviews, and from randomized exercise trials in older adults in which metformin blunted some exercise adaptations. One review describes an emerging uncertainty in the anti-aging potential of metformin.
Observational evidence on survival and cancer
A retrospective observational cohort study using UK Clinical Practice Research Datalink data reported that patients with type 2 diabetes initiated with metformin monotherapy had longer survival than matched non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both groups. This is not a randomized comparison and cannot show cause and effect.
A review of observational studies of metformin and cancer found that 13 observational studies suffered from immortal time bias and 9 had not considered time-window bias, among other time-related biases. Three studies that avoided these biases reported no effect of metformin use on cancer incidence.
A systematic review and meta-analysis of studies comparing metformin users with non-diabetics or diabetics on other therapies reported that diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio 0.93, 95% CI 0.88-0.99). The abstract does not describe the included study designs or metformin doses. It also notes that differences in baseline characteristics were observed which had the potential to bias findings, although statistical adjustments were made.
Reviews and an editorial
The review on uncertainty concluded that developments in the evidence, including replication attempts and clinical trials of metformin in individuals without type II diabetes, generally illustrate that uncertainty. Its conflict-of-interest statement lists consulting or advisory relationships between one author and Boehringer-Ingelheim and Novartis.
An editorial states there is expanding epidemiological support for the health benefits of metformin in individuals already diagnosed with overt chronic disease. It adds that it remains to be understood if these protective effects extend to those free of chronic disease.
Randomized trials in older adults
These randomized, double-blind trials tested metformin in older adults who were also doing supervised exercise training.
| Trial | What the source says |
|---|---|
| MASTERS (resistance training) | A randomized, double-blind trial gave healthy older adults 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study while all subjects performed 14 weeks of supervised progressive resistance exercise training. The authors concluded that metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. |
| Aerobic exercise training | A double-blinded trial randomized older adults to placebo (n = 26) or metformin (n = 27) during 12 weeks of aerobic exercise training (AET). The abstract does not state the dose. Metformin attenuated the increase in whole-body insulin sensitivity and VO2 max after AET. |
A proposed trial and a mechanism caution
A report from the TAME Biomarkers Workgroup describes TAME (Targeting Aging with Metformin) as a proposed randomized clinical trial using metformin to affect molecular aging pathways to slow the incidence of age-related multi-morbidity and functional decline. The excerpt used here reports no TAME results. The report's competing-interest statement says one author was the principal clinical trial investigator for studies involving Elcelyx (delayed release metformin).
A review of metformin's mechanisms says widely studied mechanisms, such as complex I inhibition leading to AMPK activation, have only been observed at supra-pharmacological (>1 mM) metformin concentrations, which do not occur in the clinical setting.
What this does not tell you
The survival comparisons were observational and compared people with diabetes taking metformin with other groups. They do not describe adults without diabetes, and the sources name possible bias: immortal time bias, time-window bias and baseline differences. The randomized trials measured exercise responses, not survival or lifespan. TAME is described as proposed, and a disclosure states a relationship without saying how or whether it affected a study.
The sources used here do not cover side effects or risks. A licensed provider decides whether any medicine fits a person's situation.