Associations of metformin and sulfonylurea on vascular complications in early‐ and late‐onset type 2 diabetes: A cohort study

Aims To compare cardiovascular and microvascular outcomes associated with metformin versus sulfonylurea therapy among patients with early‐onset (<40 years) and late‐onset (≥40 years) type 2 diabetes. Materials and Methods We conducted a population‐based cohort study of adults with newly diagnosed type 2 diabetes who initiated metformin or sulfonylurea between 2010 and 2021 in Yinzhou Health Information System (YHIS). Participants were stratified by age at diagnosis and matched 1:1 using propensity scores. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular disease (CVD) and microvascular disease (MVD). Sensitivity analyses included extended landmarks, inverse probability weighting, and negative control outcomes. Results After matching, 1267 early‐onset and 18 409 late‐onset pairs were included. Sulfonylurea use was associated with higher CVD risk than metformin, especially in early‐onset type 2 diabetes (HR = 1.69, 95% CI 1.10–2.60), with a smaller increase in late‐onset disease (HR = 1.07, 95% CI 1.02–1.13; p interaction = 0.037). MVD risks were similar between treatments across age groups. Sensitivity analyses showed consistent results. Conclusions Sulfonylurea therapy was linked to increased cardiovascular risk, particularly in younger patients, while microvascular outcomes were comparable. These findings support metformin as the preferred first‐line therapy for early‐onset type 2 diabetes.