Effect of metformin on clinically significant chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

e24151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that negatively impacts quality of life and treatment adherence in cancer patients. Preclinical studies and recent trials suggest that metformin may have neuroprotective effects in cancer patients undergoing neurotoxic chemotherapy. We performed a systematic review and meta-analysis to evaluate the effect of adding metformin to standard chemotherapy regimen on clinically significant (grade ≥2) CIPN. Methods: We systematically searched PubMed, Embase, Scopus, CENTRAL and ClinicalTrials.gov for studies assessing metformin in conjunction with neurotoxic chemotherapy. Randomized controlled trials comparing metformin versus control in cancer patients receiving neurotoxic chemotherapy and reporting grade ≥2 CIPN were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analysis of risk ratios (RR) was performed using the Mantel-Haenszel method with Hartung-Knapp adjustment. Heterogeneity was quantified with I² and tau². Prospero registration number: CRD420251248636. Results: Eight studies comprising 698 patients had reported grade ≥2peripheral neuropathy events. Metformin significantly reduced the risk of grade ≥2 CIPN compared with control (RR 0.61, 95% CI 0.51–0.74, p = 0.0005). Statistical heterogeneity was low. (I² = 0%, tau² = 0). Conclusions: Metformin is associated with a significant and consistent reduction in the risk of clinically significant CIPN, suggesting its potential as a neuroprotective adjunct during chemotherapy. Because involved studies were small and varied in chemotherapy regimens/durations; larger, high-quality randomized trials are warranted to provide conclusive evidence.