8418 Association of GLP-1 Receptor Agonists and SGLT-2 Inhibitors with Major Adverse Cardiovascular Events and Serious Liver Events among Patients with Type 2 Diabetes and MASLD

Abstract Disclosure: A. Kutz: None. D.J. Wexler: None. J. Liu: None. J.M. Paik: None. E. Patorno: None. Introduction and study question Little is known about the cardiovascular (CV) and hepatic effectiveness of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT-2i) in people with type 2 diabetes (T2D) and known metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical practice. We assessed the comparative CV and hepatic effectiveness and the safety of GLP-1 RA and SGLT-2i in people with T2D and prevalent MASLD. Methodology Using pooled data from Medicare fee-for-service (2013–2020) and a large U.S. health insurance database (2013-June 2022), we conducted two propensity-score fine stratification weighted cohort studies including adults with T2D and a diagnosis of MASLD who initiated GLP-1RA, SGLT-2i, or dipeptidyl peptidase 4 inhibitors (DPP-4i, reference). Using Cox proportional hazards models, we assessed the primary CV effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, or all-cause mortality. The primary hepatic effectiveness outcome was a composite of serious liver events (hospitalization for ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, bleeding esophageal varices, hepatic encephalopathy, or liver transplantation). The safety outcome was a composite of severe adverse events (lower limb amputation, non-vertebral fracture, emergency admission for hypoglycemia, or hospitalization for acute kidney injury, diabetic ketoacidosis DKA, severe genital or urinary tract infection, acute pancreatitis, or biliary event). Major results Compared with DPP-4i (n=17,084 initiators), the hazard ratio (HR) for the primary CV outcome associated with GLP-1 RA (n=13,666 initiators) was 0.67 (95% CI, 0.56 to 0.81), corresponding to an incidence rate difference (IRD) per 1,000 person-years of -21.6 (95% CI, -26.7 to -16.6). The HR for the primary hepatic outcome was 0.47 (95% CI, 0.25 to 0.90), the IRD -2.1 (95% CI -3.4 to -0.9). Similar CV benefits were observed for SGLT-2i (n=11,108) vs DPP-4i (n=16,979), with a HR for the primary CV outcome of 0.82 (95% CI 0.70–0.96) and an IRD of -11.0 (95% CI -16.2 to -5.8). For the primary hepatic outcome, the HR was 0.81 (95% CI 0.45 to 1.44) and the IRD -1.1 (95% CI -2.4 to 0.3). Severe adverse events were not more frequent with GLP-1RA or SGLT-2i compared with DPP-4i. Interpretation and conclusion Among people with T2D and MASLD, the use of GLP-1 RA or SGLT-2i was associated with fewer CV events, vs DPP-4i, while GLP-1 RA also reduced serious liver events. Compared with DPP-4i, GLP-1RA or SGLT-2i were not associated with higher safety adverse event rates. Presentation: 6/2/2024