Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 22875195 · doi:10.1007/s00125-012-2653-7
What was done
A systematic review and fixed-effects meta-analysis evaluated randomized controlled trials (RCTs) comparing metformin with active glucose-lowering therapy or placebo/usual care in adults. Inclusion required a minimum of 500 participants and at least 1 year of follow-up. From 4,039 screened abstracts, 14 eligible RCTs reported cancer incidence (or cancer mortality in 2 trials lacking incidence data) and all-cause mortality.
What was found
Across 11 RCTs with 398 cancer cases over 51,681 person-years, metformin showed no significant reduction in cancer risk compared to all comparators (summary RR 1.02, 95% CI 0.82–1.26), against active comparators (RR 0.98, 95% CI 0.77–1.23), or against placebo/usual care (RR 1.36, 95% CI 0.74–2.49). For all-cause mortality across 13 RCTs with 552 deaths over 66,447 person-years, the summary RR was 0.94 (95% CI 0.79–1.12).
Why it matters
These findings challenge observational studies suggesting metformin lowers cancer risk by approximately one-third, demonstrating no preventive signal in randomized trial data.
Limits
Follow-up times in the included trials were relatively short for long-latency cancer and mortality endpoints. Two trials lacked direct cancer incidence data and substituted cancer mortality. Control arms had heterogeneous comparators, and the total number of cancer events (398) provides limited statistical power for individual cancer subtypes.
Cited by
- contradicts Metformin has been shown in short-term studies to possibly prevent cancer prophylactically.