Metformin enhances survival with immune checkpoint inhibitors in cancer patients: A meta-analysis

Metformin, a primary medication for type 2 diabetes, has garnered interest due to its possible anti-tumor properties and impacts on the tumor microenvironment. This meta-analysis evaluated the impact of combining metformin with immunotherapy on overall survival (OS) and progression-free survival (PFS) in cancer patients. Relevant studies published from January 2015 to December 2024 were searched in databases such as Embase, Web of Science, PubMed and Cochrane Library. Statistical analyses were performed using STATA 18.0 software. With a total sample size of 5,014 patients, this research included 9 papers. OS and PFS were analyzed as time-to-event outcomes, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. The results indicated that metformin combined with immunotherapy significantly improves OS (HR=0.78, 95% CI: 0.62-0.97, P=0.027) and PFS (HR=0.80, 95% CI: 0.69-0.93, P=0.005) in cancer patients. Subgroup analysis revealed that the Asian population benefited more (OS: HR=0.66, 95% CI: 0.47-0.91, P=0.012; PFS: HR=0.69, 95% CI: 0.58-0.82, P<0.001), whereas the non-Asian group did not demonstrate any significant connection. The results suggest that combining metformin with immunotherapy enhances outcomes, particularly in Asian populations. However, factors such as geographic location, immunotherapy protocols and metformin dosage may influence therapeutic efficacy. Future research should explore subpopulation differences and optimize combination therapy strategies.