Aims
To evaluate the risk of all-cause mortality and major adverse cardiovascular events (MACE) for patients exposed to first-line monotherapy with sulfonylurea or metformin.
Methods
Data were from the Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with metformin or sulfonylurea monotherapy as their first-line glucose-lowering regimen 2000–2012. The primary endpoint was all-cause mortality; the secondary endpoint was MACE (myocardial infarction or stroke). Time to endpoints was compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score.
Results
In the main analysis, 76,811 patients were prescribed metformin monotherapy (mean follow-up 2.9 years) and 15,687 sulfonylurea monotherapy (mean follow-up 3.1 years). 2,048 patients were included in each arm of the directly matched cohorts and 8,836 in the propensity-matched. With respect to all-cause mortality, using all three analytical approaches the hazard ratio was significantly increased for sulfonylurea compared with metformin: adjusted HR=1.580 (95% CI 1.483–1.684) for the main analysis, 1.902 (1.733–2.088) for those matched on propensity score, and 1.272 (1.021–1.584) for the directly matched cohort analysis. For MACE the respective hazard ratios were 1.196 (1.090–1.313), 1.202 (1.001–1.442), and 0.814 (0.578–1.148), respectively.
Conclusions
All-cause mortality was significantly increased in patients prescribed sulfonylurea compared with metformin monotherapy. Whilst residual confounding and confounding by indication may remain, this study indicates that first-line treatment with sulfonylurea monotherapy should be reconsidered.
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