Case-control study of second-line therapies for type 2 diabetes in combination with metformin and the comparative risks of myocardial infarction and stroke

Abstract

We conducted a population-based case-control study to assess the myocardial infarction (MI) and stroke risks associated with sulfonylureas and insulin when used in combination with metformin. Cases had type 2 diabetes and used metformin + insulin or metformin + sulfonylureas at the time of a first MI or first stroke from 1995–2010; controls used the same treatment combinations and were randomly sampled from the same population. MI and stroke diagnoses and potential confounders were validated by medical record reviews. Compared with metformin + sulfonylurea, metformin + insulin was associated with similar risks of MI or stroke (OR 0.98 [95% CI, 0.63–1.52]). Meta-analysis with another observational study improved the precision of the risk estimate (RR 0.92 [95% CI, 0.69–1.24]). Current evidence suggests that there may not be large differences in cardiovascular risk associated with the use of insulin or sulfonylureas when used in combination with metformin.