New research from investigators at Mass General Brigham suggests that a commonly used type 2 diabetes medication is linked to a higher rate of heart-related conditions compared to medications that hit other targets. The study examined nationwide data from nearly 50,000 patients treated with different sulfonylureas and found that glipizide – the most widely used drug in the U.S. within this category – was linked to higher incidence of heart failure, related hospitalization and death compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Results are published in JAMA Network Open .
"Patients with type 2 diabetes are at heightened risk of adverse cardiovascular incidents such as stroke and cardiac arrest," said corresponding author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women's Hospital (BWH), a founding member of the Mass General Brigham healthcare system. "While sulfonylureas are popular and affordable diabetes medications, there is a lack of long-term clinical data on how they affect cardiac health in comparison to more neutral alternatives like dipeptidyl peptidase 4 inhibitors."
Turchin and co-authors emulated a target trial by analyzing electronic health records and insurance claims data from the BESTMED consortium. The cohort included 48,165 patients with type 2 diabetes and moderate cardiovascular risk who received care at 10 different study sites across the country, including BWH, as well as those 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 DPP4i in addition to metformin, a primary diabetes medication. They found that glipizide was associated with a 13% increase in cardiovascular risk when compared to DPP4i, while glimepiride and glyburide led to relatively smaller and less clear effects, respectively. The authors propose that further research is needed to uncover the underlying mechanisms.
"Our study underscores the importance of evaluating each drug in a particular pharmacological class on its own merits," said Turchin.
Authorship: In addition to Turchin, Mass General Brigham authors include Marie E. McDonnell. Additional authors include Miguel A. Hernán, Lucia C. Petito, Emma Hegermiller, Ryan Carnahan, Andrea DeVries, Satyender Goel, M. Cecilia Lansang, Vinit Nair, Elisa Priest, Vincent J. Willey, and Alan F. Kaul.
Disclosures: Turchin reported receiving grants from Eli Lilly and personal fees from Novo Nordisk and Proteomics International. Petito reported receiving grants from Omron Healthcare Co, Ltd. Lansang reported receiving grants from Abbott and Dexcom. Priest reported receiving grants from Boehringer Ingelheim, AstraZeneca, CSL Vifor, and Owkin. Willey reported being employed by Carelon Research. Hernán reported receiving personal fees from Cytel and ProPublica, being a consultant to Adigens Health (a company of which he owns equity), and being a member of the ADIALab Advisory Board; his interests were declared, reviewed, and approved by Harvard University in accordance with its institutional compliance policies. No other disclosures were reported.
Funding: This study was funded in part by the Patient-Centered Outcomes Research Institute (contract Nos. DB-2020C2-20308 and RI-MISSOURI-01-PS1).
Paper cited: Turchin, A. et al. "Cardiovascular Events in Individuals Treated With Sulfonylureas or Dipeptidyl Peptidase 4 Inhibitors." JAMA Network Open. DOI: 10.1001/jamanetworkopen.2025.23067
