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Sulfonylureas Linked to Cardio Disease in Women Without Prior Incident

Use over 10-year period also leads to cardiac events in type 2 patients using metformin monotherapy…

Cardiovascular disease is a common comorbid complication in type 2 diabetes patients. 50-80% of type 2 diabetes patient deaths are a result of a cardiovascular disease. Sulfonylureas are one of the most widely prescribed classes of antihyperglycemic medications for managing diabetes. Though their use is widespread, they have been associated with adverse effects, including weight gain, hypoglycemia and cardiovascular risks. Previous studies have shown an association between sulfonylureas and increased cardiovascular events and mortality. Many were limited by lack of control of confounders or the use of health record data without confirmation of outcomes.

This prospective study sought to identify the association between long-term sulfonylurea use and incident cardiovascular disease in type 2 diabetes patients who lacked cardiovascular disease at baseline using the Nurses’ Health Study cohort. 4,902 women with type 2 diabetes and without cardiovascular disease at baseline were selected with a follow-up period of 10 years. Cardiovascular disease end points included myocardial infarction, coronary heart disease and stroke. These events were identified using patient medical records. Cox proportional hazard models were used to generate relative risk and 95% confidence intervals to compare those using a sulfonylurea and those using a different medication class. Of the 4,902 women followed, 2,435 used a sulfonylurea and 2,467 were nonusers.

Over the 10-year follow-up period, 339 incident cases of cardiovascular disease were identified with 191 cases of coronary heart disease and 148 cases of stroke. A longer duration of sulfonylurea use was associated with an increased risk of coronary heart disease when compared to nonusers: 1-5 years of use (RR 1.24, 95% CI 0.85-1.81), 6-10 years of use (RR 1.51, 95% CI 0.94-2.42) and >10 years of use (RR 2.15, 95% CI 1.31-3.54). Those using metformin and a sulfonylurea in combination were also at increased coronary heart disease risk when compared to metformin monotherapy users (RR 3.27, 95% CI 1.31-8.17). An association between sulfonylurea use and stroke was not observed.

The results of this study show an association between increased duration of sulfonylurea use and cardiovascular disease risk. Those continuously using a sulfonylurea for over 10 years were at nearly a two times greater risk for coronary heart disease than non-users. Those using metformin and sulfonylurea combination therapy were also at increased coronary heart disease risk compared to metformin monotherapy users. Further studies are needed to determine if these results can be replicated, particularly when both sexes are included.

Practice Pearls:
Previous studies have shown an association between the use of sulfonylureas and cardiovascular disease risk.
Use of a sulfonylurea for greater than 10 years was associated with a higher risk of coronary heart disease development.
Sulfonylurea use in combination with metformin was also found to be associated with coronary heart disease when compared to those using metformin as monotherapy.

Li Y, Hu Y, Ley SH, Rajpathak S and Hu FB. Sulfonylurea Use and Incident Cardiovascular Disease Among Patients with Type 2 Diabetes: Prospective Cohort Study Among Women. Diabetes Care. 2014.