Metformin monotherapy versus predominantly older non‐metformin antidiabetic medications for cerebrovascular risk in early type 2 diabetes management

Abstract Aim Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first‐line monotherapy (metformin or non‐metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. Methods We analysed 9090 patients with T2D without complications who were prescribed either metformin or non‐metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. Results Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non‐users ( p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67‐0.69) and severe events (aHRs: 0.67‐0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73‐0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62‐0.94, p < .0001), indicating a dose‐dependent effect. Conclusion Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early‐stage T2D, highlighting its dose‐dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.