Abstract 4366311: Cardiovascular-Kidney-Metabolic Syndrome: Comparing Outcomes between Sodium glucose co-transporter 2 inhibitor and Glucagon like petide 1 receptor analogue use - A Real world propensity Matched Analysis

Introduction: Cardiovascular-Kidney-Metabolic (CKM) syndrome, defined by the interplay of cardiovascular disease, chronic kidney disease, and metabolic dysfunction, is common yet underdiagnosed due to a lack of formal criteria. The 2023 AHA advisory highlights the need for identifying therapies that reduce cardiovascular risk and mortality in this high-risk population. SGLT-2 inhibitors and GLP-1 agonists have shown cardiovascular benefit beyond glycemic control. However, it remains unclear whether one of these drug classes offers superior protection against major adverse cardiovascular events (MACE) in patients with CKM syndrome. Research Question/Hypothesis: Given the established cardiovascular and mortality benefits of SGLT2i and the emerging evidence supporting GLP-1RA in reducing MACE, we aim to compare the effectiveness of these two therapeutic classes in patients with CKM syndrome. We hypothesize that one class may confer a superior reduction in MACE incidence within this high-risk population. Methods: We conducted a retrospective, propensity-matched analysis using real world data from the TriNetX US database that compared patients with CKM syndrome who were treated with either GLP1 analogues or SGLT2 inhibitors. We compared the outcomes of hospitalization, all-cause mortality, and first instances of heart failure and atrial fibrillation. Results: Our analysis revealed a statistically significant difference in outcomes, favoring GLP1 RA over SGLT2 inhibitors. We found that GLP1 RA’s were associated with lower risks for hospitalization (RR 0.751, 95% CI 0.728-0.775, p<0.001), mortality (RR 0.61, 95% CI 0.565-0.658, p<0.001), Incident heart failure (RR0.762, 95% CI 0.661-0.878, p< 0.001), incident atrial fibrillation (RR 0.666, 95% CI 0.577-0.768, p<0.001). Conclusion: In our limited dataset, treatment with GLP-1RA was associated with a lower risk of all-cause hospitalizations and mortality, incident heart failure, and incident atrial fibrillation when compared to SGLT2 inhibitors in patients with CKM syndrome, over a 1-year follow –up period. These findings beg the question- can GLP-1RA offer broader protection against cardiovascular risk in this population? Further studies with larger datasets and extended follow-up durations are warranted to validate these findings and better define the therapeutic benefit and role of GLP-1RA in CKM syndrome management.