1670-P: Heterogeneity of Treatment Effect of Glucagon-Like Peptide 1 Receptor Agonists for Primary Prevention of Cardiovascular Events in Type 2 Diabetes

Introduction and Objective: GLP-1RA have emerged as a mainstay T2DM treatment. These agents reduce cardiovascular risk, but sources of heterogeneous treatment effects are not known. Methods: This was a retrospective cohort study, using a new-user, active-comparator target trial emulation approach. The primary exposure was prescription of a GLP-1 RA. The comparator was prescription of any SGLT2i or DPP-IVi. The primary end point was time to first major adverse cardiovascular/cerebrovascular event (MACCE). Propensity score overlap weighting combined with LASSO was used to balance patient characteristics— including medical history, laboratory/physical measures, and social determinants of health— and estimate causal subgroup effects. Results: In total, 506,432 patients without a history of cardiovascular disease were prescribed a GLP-1RA and 648,505 were prescribed a SGLT2i or DPP-IVi. Estimated treatment effects are shown in Figure 1. In summary, GLP-1RA prescription was associated with a reduction in MACCE risk for female patients, patients age 18-44 and 65+, Black patients, non-Hispanic patients, and patients at high PREVENT-estimated CVD risk. Conclusion: While confidence intervals were wide, it is possible that GLP-1RA prescription may be differentially associated with MACCE risk reduction across subgroups, especially for female patients, who derived greater benefits than male patients. Disclosure J.B. Lusk: None. J. Shin: None. L. Wilson: Research Support; Ended; Pfizer Inc., Bristol-Myers Squibb Company. C. Powell: None. P. Madala: None. E. OBrien: Research Support; Current; Pfizer Inc. F. Li: None. B. Mac Grory: None. Funding American Heart Association Data Science (25GLP1450119), National Institutes of Health (P30AG072958)