Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials

Background: To investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age >= 18). Methods: Databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) and clinical trial registries (; the World Health Organization International Clinical Trials Registry Platform) were screened for randomized, controlled trials (RCT) reporting at least progression-free survival (PFS) and/or overall survival (OS). Main outcome measures included hazard ratios (HR), and combined HRs and 95% confidence intervals (CI) were calculated using random-effects models. Results: Of the 8419 records screened, 22 RCTs comprising 5943 participants were included. Pooled HRs were not statistically significant in both PFS (HR 0.97, 95% CI 0.82-1.15, I-2 = 50%) and OS (HR 0.98, 95% CI 0.86-1.13, I-2 = 33%) for patients with cancer between the metformin and control groups. Subgroup analyses demonstrated that metformin treatment was associated with a marginally significant improvement in PFS in reproductive system cancers (HR 0.86, 95% CI 0.74-1.00) and a significantly worse PFS in digestive system cancers (HR 1.45, 95% CI 1.03-2.04). The PFS or OS was observed consistently across maintenance dose, diabetes exclusion, median follow-up, risk of bias, and combined antitumoral therapies. Conclusion: Metformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but was related to a worse PFS in digestive system cancers.

Automated summary

This study investigates the effect of metformin treatment on the prognosis of different types of cancer. The results suggest that metformin treatment is not associated with cancer-related mortality, but may have beneficial effects on patients with reproductive system cancers and worsen the prognosis for patients with digestive system cancers.