Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Network Open, 8(7), e2523067. https://doi.org/10.1001/jamanetworkopen.2025.23067 Dr. Alexander Turchin et al.
Points
- This comparative study analyzed data from 48,165 type 2 diabetes patients with moderate cardiovascular risk who were taking metformin.
- Researchers compared cardiovascular outcomes for patients starting a sulfonylurea (glipizide, glimepiride, or glyburide) versus a dipeptidyl peptidase-4 inhibitor.
- Patients taking glipizide demonstrated a 13% higher risk of major adverse cardiovascular events over five years compared to those taking DPP-4 inhibitors.
- The study observed that glimepiride and glyburide were associated with smaller and statistically less clear increases in cardiovascular risk compared to glipizide.
- These findings indicate glipizide may not be the optimal second-line agent for treating type 2 diabetes in patients at moderate cardiovascular risk.
Summary
This comparative effectiveness research study aimed to emulate a target trial to assess the cardiovascular risk associated with individual sulfonylureas versus dipeptidyl peptidase 4 inhibitors (DPP4is). The study utilized electronic health records and insurance claims from 48,165 individuals with type 2 diabetes (T2D) and moderate cardiovascular risk who initiated a second-line agent after metformin. The cohort had a median age of 61 years, comprising 47.1% female participants, with a median HbA1c level of 7.8%, and was followed for a median duration of 37 months. Participants were categorized by the initiation of glipizide (n=18,147), glimepiride (n=14,282), glyburide (n=1,887), or a DPP4i (n=13,849).
The primary outcome was a 4-point composite of major adverse cardiovascular events (MACE-4), including myocardial infarction, ischemic stroke, heart failure hospitalization, or cardiovascular death. Over the follow-up period, 6.6% of individuals experienced a MACE-4 event. The estimated 5-year risk of MACE-4 was 8.1% (95% CI, 7.5%-8.7%) for DPP4is, 8.4% (95% CI, 6.8%-9.9%) for glyburide, 8.6% (95% CI, 7.9%-9.2%) for glimepiride, and 9.1% (95% CI, 8.7%-9.7%) for glipizide.
Compared with the DPP4i reference group, the 5-year risk ratio of MACE-4 was statistically significant only for glipizide at 1.13 (95% CI, 1.03-1.23). The risk ratios for glimepiride (1.07; 95% CI, 0.96-1.16) and glyburide (1.04; 95% CI, 0.83-1.24) were not statistically significant. The findings suggest that among sulfonylureas, glipizide is associated with a higher risk of MACE-4 and may not be an optimal agent for T2D patients with moderate cardiovascular risk.
Link to the article: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2836782
References Turchin, A., Petito, L. C., Hegermiller, E., Carnahan, R., DeVries, A., Goel, S., Lansang, M. C., McDonnell, M. E., Nair, V., Priest, E., Willey, V. J., Kaul, A. F., & Hernán, M. A. (2025). Cardiovascular events in individuals treated with sulfonylureas or dipeptidyl peptidase 4 inhibitors. JAMA Network Open, 8(7), e2523067. https://doi.org/10.1001/jamanetworkopen.2025.23067
