The safety and efficacy of metformin on metabolic syndrome parameters in prostate cancer patients receiving androgen deprivation therapy: A systematic review and meta-analysis

BACKGROUND: Prostate cancer patients are more likely to develop metabolic syndrome because androgen deprivation therapy (ADT), a standard treatment for advanced prostate cancer, causes major metabolic syndrome components and associated disorders. Metformin, a low-cost oral antidiabetic with a favorable safety profile, may be useful for preventing metabolic issues associated with ADT. This meta-analysis aims to assess the efficacy and safety of metformin on metabolic syndrome parameters in prostate cancer patients receiving ADT. METHODS: In November 2025, we conducted a systematic search of PubMed, Scopus, and the Cochrane Library for randomized and non-randomized controlled trials. Studies were considered eligible if they included adult men (≥18 years) with prostate cancer receiving ADT and assessed metformin versus placebo/standard care on metabolic outcomes. For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1+563 using a random-effects mode. RESULTS: We included ten trials with a total sample size of 2,642 patients. There were no significant differences in HbA1c (MD = -0.01, 95% CI -0.1; 0.2, P = 0.8), body weight (MD = 0.42, 95% CI -3.31; 4.16, P = 0.8), body mass index (MD = -0.01, 95% CI -0.1; 0.2, P = 0.8), or waist circumference (MD = -1.67, 95% CI -4.6; 1.26, P = 0.26). There was no significant difference in blood pressure, fasting glucose, triglycerides, or HDL cholesterol levels. Metformin was well tolerated but was related with a greater risk of diarrhea (RR = 2.55, 95% CI 1.02; 6.39). The Trial sequential analysis (TSA) stated that the current evidence is insufficient and underpowered. CONCLUSION: According to our data, metformin did not provide a substantial improvement in metabolic syndrome indices for prostate cancer patients on ADT. Its efficacy as a stand-alone remedy appears to be limited. Future large-scale clinical trials should investigate the role of metformin in combination with structured lifestyle changes.