Abstract
295-OR: Cardiovascular Events in Patients Treated with Sulfonylureas—A Target Trial Emulation
Diabetes (New York, N.Y.), Vol.74(Supplement_1)
06/20/2025
DOI: 10.2337/db25-295-OR
Abstract
Introduction and Objective: Sulfonylureas are a common choice in treatment of type 2 diabetes (T2D). Cardiovascular safety of sulfonylureas is unknown.
Methods: We emulated a target trial using observational data from 12 health systems and insurance plans across the US. Eligible individuals were patients with T2D and hyperglycemia (HbA1c 7.0-11.0% or equivalent glucose levels) at moderate CV risk (no prior CV disease) on metformin monotherapy who initiated a second T2D medication between 01/01/13 and 12/31/22, with eGFR ≥ 45 ml/min/1.73m2 and with no contraindications to study medications. We compared patients initiating individual sulfonylureas (glimepiride, glipizide and glyburide) to patients initiating DPP4i (which were shown in multiple controlled trials to have CV risk similar to placebo). In each treatment arm we estimated the 5-year risk of a composite outcome (MI, ischemic CVA, HF hospitalization or CV death) after adjustment for demographics, comorbidities and laboratory values at baseline.
Results: We studied 48,165 patients followed for a median of 37 (IQR 20-64) months, with a median age of 61 (IQR 52-69) years and median baseline HbA1c of 7.8% (IQR 7.3-8.5%). Of these, 13,849 patients initiated a DPP4i; 14,282 initiated glimepiride; 18,147 initiated glipizide; and 1,887 initiated glyburide. A total of 3,158 (6.6%) of patients experienced the primary outcome endpoint. The estimated 5-year risk ratios (95% CI), compared to DPP4i, were 1.04 (95% CI 0.83 to 1.24) for glyburide, 1.07 (95% CI 0.96 to 1.16) for glimepiride and 1.13 (95% CI 1.03 to 1.23) for glipizide. Sensitivity analysis excluding saxagliptin from the reference DPP4i category showed similar results.
Conclusion: Patients with T2D treated with glipizide as a second agent after metformin had the highest incidence of MACE-4 events compared with patients treated with DPP4i among those initiating a sulfonylurea. Glipizide may not be the optimal agent in treatment of patients with T2D at elevated CV risk.
Details
- Title: Subtitle
- 295-OR: Cardiovascular Events in Patients Treated with Sulfonylureas—A Target Trial Emulation
- Creators
- ALEXANDER TurchinLUCIA PetitoEMMA HegermillerRYAN M. CarnahanANDREA R. DevriesSATYENDER GoelMARIE E. McdonnellM Cecilia LansangVINIT NairELISA L. PriestVINCENT WilleyALAN F. KaulMIGUEL Hernan
- Resource Type
- Abstract
- Publication Details
- Diabetes (New York, N.Y.), Vol.74(Supplement_1)
- DOI
- 10.2337/db25-295-OR
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Publisher
- AMER DIABETES ASSOC
- Grant note
- PCORI: DB-2020C2-20308
PCORI (DB-2020C2-20308)
- Language
- English
- Date published
- 06/20/2025
- Academic Unit
- Epidemiology; Nursing; Injury Prevention Research Center
- Record Identifier
- 9984843748002771
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