Cardiovascular Events in Individuals Treated With Sulfonylureas or Dipeptidyl Peptidase 4 Inhibitors
An erratum to this article was published (JAMA Netw Open, 1 Dec 2025 ↗)
Authors' conclusion
In this comparative effectiveness research study of sulfonylureas vs DPP4i in patients with T2D, the risk of MACE-4 events was highest for glipizide. These findings suggest that sulfonylureas, glipizide in particular, may not be the optimal agent in treatment of individuals with T2D at moderate cardiovascular risk.
Study context
- Population
- Individuals with T2D and moderate cardiovascular risk on metformin monotherapy, 10 US health systems or 2 large insurance plans, 2014–2023; median age 61 years, 47.1% female, median HbA1c 7.8%
- Participants
- 48,165 eligible individuals
- Comparison
- Individual SUs vs DPP4i as second-line therapy after metformin
- Glipiziden = 18,147
- Glimepiriden = 14,282
- Glyburiden = 1,887
- DPP4in = 13,849reference
- Outcome
- MACE-4: MI, ischemic stroke, HF hospitalization or cardiovascular death
- Follow-up
- 5 years
Methodological detailstarget trial emulation, 10 US health systems and 2 health insurance plans, Data analyzed July 2024 to March 2025
- Target trial emulation
- 10 US health systems and 2 health insurance plans
- Data analyzed July 2024 to March 2025
Main finding
As reported in the abstract
MACE-4 · 5-year risk
Each group vs DPP4i5-year RR (95% CI)
Glipizide
1.13(1.03–1.23)
Glimepiride
1.07(0.96–1.16)
Glyburide
1.04(0.83–1.24)
Further findings
Major adverse cardiovascular events (MACE-4) events overall · median follow-up 37 (IQR 20-64) months
- Individuals with a MACE-4
- 3158 (6.6%)
Original publication
Cardiovascular Events in Individuals Treated With Sulfonylureas or Dipeptidyl Peptidase 4 Inhibitors. JAMA Netw Open. Published 1 July 2025. doi:10.
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