A new study from investigators at Mass General Brigham suggests that commonly used type 2 diabetes drugs are associated with a higher percentage of heart-related conditions compared to drugs that collide with other targets. In this study, we looked at national data from nearly 50,000 patients treated with different sulfonylureas, and found that Glipizide, the most widely used drug in the United States within this category, had a higher incidence of heart failure, associated hospitalizations, and death compared to dipeptidylpeptidase-4 (DPP-4) inhibitors. The results are published in Ingama Network Open.
Patients with type 2 diabetes are at an increased risk of harmful cardiovascular accidents, such as stroke and cardiac arrest. Sulfonylureas are a common and affordable diabetic drug, but there is a lack of long-term clinical data on how they affect heart health compared to more neutral alternatives such as dipeptidylpeptidase 4 inhibitors. ”
Alexander Turchin, MD, MS, Corresponding authors Brigham and Women's Hospital (BWH)'s Endocrine Division
Turchin and co-authors emulated the target trial by analyzing electronic health records and insurance claim data from the BestMed Consortium. The cohort included 48,165 patients with type 2 diabetes and moderate cardiovascular risk who were treated with care at 10 different study sites across the country, including BWH, and patients covered by two different national health insurance plans.
The researchers studied the five-year risk of major adverse cardiovascular events in patients treated with different sulfonylureas (glimepiride, glipizide or glyburide or glyburide) or DPP4I, in addition to metformin, the leading diabetic drug. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4I, but glimepiride and glyburide each had relatively small and less clear effects. The authors suggest that further research is needed to uncover the underlying mechanism.
“Our research highlights the importance of assessing each drug in a particular pharmacological class with its own merit,” Tarkin said.
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Journal Reference:
Turchin, A., et al. (2025). Cardiovascular events in individuals treated with sulfonylurea or dipeptidylpeptidase 4 inhibitors. Jama Network opens. doi.org/10.1001/jamanetworkopen.2025.23067.
