1266-P: The Risk of Major CV Events after Initiation of SGLT2i, GLP-1RA, DPP-4i, or SUs in Patients with Type 2 Diabetes and Low-to-Moderate CV Risk

Introduction & Objective: We assessed the risk of major CV events (MACE) after initiation of SGLT2 inhibitors (SGLT2i), GLP1 receptor agonists (GLP-1RA), DPP-4 inhibitors (DPP-4i), or sulfonylurea (SU) in patients with T2D and low-to-moderate CV risk, for whom limited guidance exists on which diabetes medications clinicians should prescribe. Methods: Using Medicare and 2 U.S. private health plans (2013-2023), we identified six pairwise cohorts of 1:1 propensity score-matched patients aged ≥18 years (≥66 years in Medicare) with T2D and no established CV disease, initiating SGLT2i, GLP-1RA, DPP-4i, or SU (Table). Our primary outcome was MACE, i.e., myocardial infarction (MI), stroke, or mortality. We estimated HRs and 95% CIs, adjusting for 156 covariates. Results: Compared to DPP-4i or SUs, SGLT2i and GLP-1RA were associated with 15-28% reductions in the risk of MACE (Table), over a mean follow-up of ~11 months. Compared with GLP-1RA, SGLT2i were associated with a small increase in the risk of MACE (HR=1.06; 95% CI=1.01-1.11), driven by a 13% increase in risk of MI. Compared with SUs, DPP-4i had a 10% decrease in the risk of MACE. Conclusion: This study suggests robust reductions in rates of MACE with SGLT2i and GLP-1RA compared to DPP-4i or SUs in patients with T2D and no CV disease. Although differences were not large, the risk of MACE was lower with GLP-1RA (vs SGLT2i) and DPP-4i (vs SUs). Disclosure E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute. H. Tesfaye: None. C. Alix: None. E.C. DiCesare: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. B.M. Everett: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Ipsen Pharmaceuticals, Provention Bio, Inc. R. Glynn: Research Support; Amarin Corporation, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. D.J. Wexler: Other Relationship; Novo Nordisk. J.M. Paik: None. Funding Patient Centered Outcomes Research Institute (DB-2020C2-20326)