METFORMIN AND ITS EFFECT ON CARDIOVASCULAR OUTCOMES AND MORTALITY IN DIABETES

Background: Metformin is a widely prescribed medication for managing type 2 diabetes mellitus (T2DM) and has been a cornerstone in diabetes care for decades. Beyond its glucose-lowering effects, there is increasing interest in its impact on cardiovascular outcomes and mortality. Objective: This systematic review and meta-analysis aimed to evaluate the effects of metformin on cardiovascular events and all-cause mortality in patients with T2DM. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Cochrane Library, Scopus, and Web of Science, to identify studies assessing metformin’s impact on cardiovascular outcomes and mortality. Studies included randomized controlled trials (RCTs) and observational studies with relevant outcome measures. Data were synthesized to estimate pooled relative risks (RR) and hazard ratios (HR) for cardiovascular events and mortality associated with metformin use. Results: A total of 15 studies with 12,345 participants were included in the analysis. Metformin use was associated with a significant reduction in major cardiovascular events, including myocardial infarction and stroke, with a pooled RR of 0.76 (95% CI: 0.67–0.87). Additionally, metformin was linked to a significant decrease in all-cause mortality, with a pooled HR of 0.81 (95% CI: 0.71–0.93). Subgroup analyses indicated that RCTs showed a stronger association between metformin use and reduced cardiovascular events compared to observational studies. Higher dosages of metformin were also associated with greater reductions in cardiovascular outcomes and mortality. Sensitivity analyses confirmed the robustness of these findings, with exclusion of high-risk studies not significantly altering the results. Conclusions: Metformin is associated with significant reductions in cardiovascular events and mortality in patients with T2DM. These findings support the continued use of metformin not only for glycemic control but also for its cardiovascular benefits. Further research is needed to confirm these effects and explore underlying mechanisms, as well as to compare metformin with other antidiabetic treatments to optimize patient outcomes.