Original Investigation

Cardiovascular Events in Individuals Treated With Sulfonylureas or Dipeptidyl Peptidase 4 Inhibitors

JAMA Network Open 10.1001/jamanetworkopen.2025.23067

July 24, 2025 at 11:00 AM EDT

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Do any sulfonylureas (glimepiride, glipizide, or glyburide) associated increase the risk of cardiovascular events compared with dipeptidyl peptidase 4 inhibitors (DPP4is)?In this comparative effectiveness research study of electronic health records and claims from 48 165 individuals starting a second T2D agent after metformin, individuals treated with glipizide had a higher risk of a composite end point of myocardial infarction, ischemic stroke, heart failure hospitalization, and cardiovascular death than those treated with a DPP4i.These findings suggest that sulfonylureas, glipizide in particular, may not be the optimal agents in treatment of individuals with T2D at moderate cardiovascular risk.

Corresponding Author: Alexander Turchin, MD, MS, Division of Endocrinology, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115 (aturchin@bwh.harvard.edu).

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