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Long-term Use of Sulfonylureas and the Risk of CVD

Diabetic women who use sulfonylureas for a long time could have a higher risk of developing CHD…. 

For many years, sulfonylureas have been recommended by the American Diabetes Association as a second line therapy for the treatment of type 2 diabetes. Despite its usefulness in glycemic control, sulfonylureas can potentially produce many adverse effects such as weight gain and increased cardiovascular risk. Currently, approved package labels for all sulfonylureas are required to have a warning for increased cardiovascular risk. However, according to Dr. Yanping Li from the department of Nutrition at Harvard School of Public Health in Boston, Massachusetts, evidence for the association between sulfonylurea use and risk of cardiovascular disease among diabetic patients is inconsistent.

To assess this association, Dr Li and colleagues conducted a prospective cohort study in which they followed 4,902 women (mean age 68 years) with diabetes (mean duration 11 years) for a 10-year period. All of the women were free of cardiovascular disease at baseline, and their use of sulfonylureas and other medications was self-reported.

During 5-10 years of follow-up, 339 incident cases (191 cases of CHD and 148 cases of stroke) were documented. The multivariable-adjusted RRs of total cardiovascular diseases for diabetic patients who had been using sulfonylurea therapy for 1-5, 6-10 and >10 years were 1.2 (95%CI 0.91-1.58), 1.4 (95%CI 0.98-1.99) and 1.65 (95%CI 1.12-2.43).

When assessing the association of sulfonylureas with CHD and stroke, the researchers found that the duration of sulfonylurea use was only significantly associated with CHD risk (p = 0.005). In addition, the RR for CHD was 3.27 (1.31-8.17) in diabetic patients who were treated with the combination of metformin and sulfonylurea compared to metformin monotherapy.

The researchers said that the results of their study were consistent with previous reports from other retrospective observational studies. They also said that this study had a lot of strengths such as its prospective study design, large sample size, long duration of follow-up, and validated cardiovascular outcome using medical records. Nonetheless, the researchers suggested that more prospective cohort studies should be done to warrant their findings.

Practice Pearls:
  • Long-term use of sulfonylureas could increase CHD risk in diabetic women.
  • There might be a significant association between duration of sulfonylurea use and CHD risk.
  • No significant association between duration of sulfonylurea use and stroke risk has been observed.

Li Y, Hu Y, Ley S. Sulfonylurea use and incident cardiovascular disease among patients with type 2 diabetes: Prospective cohort study among women. Diabetes Care 2014; doi:10.2337/dc14-1306.