Work

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

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Introduction 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. Methods 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 I 2 values. Subgroup and sensitivity analyses were also performed. Results 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, I 2 = 36.1%) or OS (HR = 1.20, 95% CI: 0.88–1.62, I 2 = 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. Conclusion 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. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier, CRD2025105994.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1752095

Authors: Shasha Zhang, Bin Chen, Xia Hu, Shiquan Hu, Yang Li, Jinbiao Han

Institutions: Sichuan University, West China Second University Hospital of Sichuan University

Language: English

Topic: Metabolism, Diabetes, and Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801