Abstract 11983: Oral Therapies for Type 2 Diabetes in Combination With Long-acting Insulin and the Risks of Myocardial Infarction and Stroke

Introduction/Hypothesis: The use of oral therapies in combination with insulin for the treatment of type 2 diabetes is common, but the cardiovascular risks or benefits are largely unknown. Among users of long-acting insulin, we conducted a population-based case-control study to evaluate the incident myocardial infarction (MI) and incident stroke risks associated with sulfonylurea and metformin use. We hypothesized that sulfonylurea use would be associated with elevated risk and metformin use with decreased risk. Methods: Cases were enrollees of Group Health Cooperative (GHC) with type 2 diabetes who used long-acting insulin at the time of diagnosis with a first MI (n=413) or first stroke (n=247) from 1995-2010. Controls (n=443) were randomly sampled GHC enrollees with type 2 diabetes who used long-acting insulin, matched to cases on age, sex, and calendar year. Sulfonylureas and metformin use was classified as current, past, or never using electronic pharmacy records. MI and stroke diagnoses and potential confounding variables were validated by medical record review. Analyses were adjusted for matching variables and cardiovascular risk factors, including smoking, duration of diabetes, blood pressure, and cholesterol. Results: Current use of sulfonylureas compared with never use was associated with a higher risk of MI (OR 1.67; 95% CI, 1.10-2.55) but not stroke (OR 1.22; 95% CI, 0.74-2.00). Current use of metformin compared with never use was associated with a lower risk of stroke (OR 0.54; 95% CI, 0.31-0.95) but not MI (OR 0.77; 95% CI 0.44-1.33). Past use of sulfonylureas and past use of metformin were not associated with either outcome. Findings were robust to sensitivity analyses that tested assumptions about eligibility criteria and medication adherence. An unmeasured confounder associated with a 2-fold increased MI risk would have to be present in 70% more current users than never users of sulfonylureas to render the sulfonylurea-MI odds ratio null. Conclusions: The use of sulfonylureas in combination with long-acting insulin may increase the risk of MI compared with insulin alone. Our study adds to a growing body of evidence that metformin may be an effective cardiovascular disease prevention therapy, even when used with insulin.