Drug Pipeline
META ANALYSIS
● Meta-analysis
Metformin with standard therapy shows no significant survival benefit in gynecologic cancers
Frontiers in Medicine
Published March 31, 2026
DOI ↗
This systematic review and meta-analysis examined 5 randomized controlled trials involving 705 patients with gynecologic malignancies (cervical, endometrial, and ovarian cancers). The analysis compared metformin combined with standard therapy against standard therapy alone, with progression-free survival and overall survival as primary outcomes.
For the overall population, metformin did not significantly improve progression-free survival (hazard ratio 0.76, 95% CI: 0.55–1.03) or overall survival (HR 1.20, 95% CI: 0.88–1.62). Subgroup analyses showed no survival benefits in patients with cervical or endometrial cancer. Sensitivity analyses confirmed the robustness of these findings.
A single study in ovarian cancer suggested possible progression-free survival improvement (HR 0.24, 95% CI: 0.09–0.65), but the wide confidence interval indicates limited reliability. Safety and tolerability data were not reported in the meta-analysis. Key limitations include the wide confidence interval for the ovarian cancer result and the fact that this finding came from only one study.
For clinical practice, current evidence does not demonstrate significant survival benefits from adding metformin to standard therapy for gynecologic malignancies. The potential signal in ovarian cancer requires confirmation in larger, dedicated trials before any clinical application can be considered.
When you're fighting a gynecologic cancer like cervical, endometrial, or ovarian cancer, you and your doctors want every possible tool. Researchers looked at whether adding a common, inexpensive diabetes drug called metformin to standard treatments could be one of those tools. They combined data from five clinical trials involving 705 patients. The bottom line: adding metformin did not significantly improve how long patients lived without their cancer getting worse (progression-free survival) or how long they lived overall (overall survival).
Digging deeper, the analysis found no survival benefit for women with cervical or endometrial cancers. For ovarian cancer, the picture was murkier. One study within the analysis suggested metformin might help delay cancer progression, but the result came with a big asterisk. The statistical confidence interval was very wide, which means the finding isn't reliable enough to bank on—it could easily be due to chance.
It's important to know this review didn't report on side effects or how well patients tolerated the combined treatment, so we don't have the full safety picture. The researchers also noted the major limitation with the potential ovarian cancer finding: that wide confidence interval makes it shaky ground for any conclusions. Right now, the combined evidence from these trials simply doesn't show that metformin boosts survival for these cancers. The search for effective new treatment combinations continues.
What this means for you: Current evidence does not show metformin improves survival for gynecologic cancers.
View Original Abstract ↓
IntroductionGynecologic 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.MethodsEmbase, 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.ResultsFive 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.ConclusionCurrent 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 Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier, CRD2025105994.
