Efficacy of metformin as an adjuvant therapy in gynecologic malignancies: a meta-analysis of randomized controlled...

Gynecologic malignancies, such as cervical, endometrial, and ovarian cancers, are among the most prevalent and lethal cancers in women worldwide. Preclinical and epidemiological studies suggest that metformin may exert antitumor effects. However, its clinical efficacy in gynecologic malignancies remains uncertain. Hence, exploring the effects of metformin in prolonging progression-free survival (PFS) and overall survival (OS) in gynecological malignancies is crucial for guiding future clinical practice. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the effect of metformin combined with standard therapy on PFS and OS in individuals with gynecologic malignancies.

Embase, the Cochrane Library, Web of Science, and PubMed were searched from database inception to 13 June 2025. RCTs meeting predefined PICOS criteria were included. Two investigators independently screened the studies, extracted data, and assessed the quality of eligible studies. Stata 15.1 was utilized to carry out meta-analyses, and random- or fixed-effects models were selected according to I² values. Subgroup and sensitivity analyses were also performed.

Five RCTs involving 705 patients were included. The overall analyses demonstrated that metformin combined with standard therapy did not significantly improve PFS (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.55-1.03, I² = 36.1%) or OS (HR = 1.20, 95% CI: 0.88-1.62, I² = 0.0%) compared with the control group. Subgroup analyses demonstrated no survival benefits in individuals with cervical or endometrial cancer. Only one study on ovarian cancer suggested that metformin might improve PFS (HR = 0.24, 95% CI: 0.09-0.65). However, the wide CI indicated limited reliability of the results. Sensitivity analyses confirmed the robustness of the findings.

Current evidence from RCTs demonstrates that metformin combined with standard therapy can not significantly improve PFS or OS in individuals with gynecologic malignancies. Further larger, multicenter, long-term RCTs are warranted to evaluate the potential benefits of metformin in individuals with metabolic abnormalities and its combined use with novel therapies.

https://www.crd.york.ac.uk/PROSPERO/, identifier, CRD2025105994.