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

Zhang S, Chen B, Hu X, Hu S, Li Y, Han J

Frontiers in pharmacology, 2026

705 participants

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 I2 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, I2 = 36.1%) or OS (HR = 1.20, 95% CI: 0.88-1.62, I2 =…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 705 participants or records.

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