Survival and Radiotherapy-Related Adverse Events in Patients Receiving Radiotherapy and Concurrent Metformin: A Systematic Review and Meta-Analysis of Randomised Controlled Trials and Cohort Studies.

Background: It remains unclear whether metformin, a widely used antidiabetic medication, has any influence on the survival outcomes or treatment-related toxicities of radiotherapy in cancer patients. Given metformin's potential anti-cancer properties, including its ability to inhibit tumour growth through the modulation of cellular metabolism and enhancement of radiosensitivity, its impact on radiotherapy outcomes warrants thorough investigation. This study aimed to evaluate the impact of metformin on survival and adverse events among cancer patients receiving radiotherapy. Methods: Database searches were conducted in MEDLINE, EMBASE, Web of Science, Scopus, and PubMed (2000-2025) to retrieve studies of adults with cancer treated with radiotherapy and concurrent metformin. Metformin users were compared with non-users. The pooled overall survival rate was presented in terms of odds ratio (OR) and 95% confidence interval (95%CI). Diabetic subgroup analyses and meta-regression by cancer type were conducted. ORs and 95%CIs of radiotherapy-related adverse events were presented by cancer type. Results: This study identified 25 articles. The pooled overall survival rate showed no significant difference between metformin users and non-users across subgroups (ORs: 1.00-1.77). Conflicting survival trends were observed for prostate, oesophageal, and non-small cell lung cancer across diabetic conditions. Metformin users with breast cancer exhibited a significantly lower risk of heart failure (OR: 0.72; 95%CI: 0.56-0.94) and heart events (OR: 0.72; 95%CI: 0.59-0.88). Conclusions: Metformin did not significantly impact overall survival but may reduce heart-related adverse events in breast cancer patients based on limited data. Further research is needed on cancer types and diabetic conditions.