AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiovascular Outcomes in Patients with Fatty Change of Liver Treated with Combined GLP-1 RA and SGLT2 Inhibitor Therapy versus GLP-1 RA Alone: A Propensity Score Matched TriNetX Analysis
By Azhar MJ, Altaf A, Alokozay E et al.
Background: Fatty change of the liver is strongly associated with cardiovascular risk due to insulin resistance, dyslipidemia, and systemic inflammation. GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2is) each provide independent cardiovascular benefits. This study assesses whether combination therapy provides additional cardiovascular protection compared with GLP-1 RA monotherapy in adults with liver fatty change and cardiometabolic comorbidities. Research Question: Does combination GLP-1 RA + SGLT2i reduce MACE risk myocardial infarction (MI), stroke, heart failure (HF), and all cause mortality compared to GLP-1 RA monotherapy in patients with fatty change of liver and cardiometabolic comorbidities? Methods: This retrospective cohort study used TriNetX, a federated network that captures data from 171 healthcare organizations. Adults (≥18 years) with fatty change of liver (ICD-10: K76.0) and ≥1 cardiometabolic comorbidity (hypertension, diabetes mellitus, dyslipidemia, or obesity) were included. Patients with competing liver etiologies (cirrhosis, alcoholic liver disease, autoimmune hepatitis, viral hepatitis, hemochromatosis, or Wilson’s disease) or prior MACE were excluded. Cohort 1: GLP-1 RA + SGLT2i (n=17,568); Cohort 2: GLP-1 RA monotherapy (n=17,568). Propensity score matching balanced cohorts on demographics, comorbidities, and medications. Outcomes were assessed via risk proportions, Kaplan-Meier survival analysis, and Cox proportional hazards modeling. A p-value <0.05 was considered statistically significant. Results: All-cause mortality occurred in 1.5% vs. 1.8%, MI in 1.3% vs. 1.4%, stroke in 1.2% vs. 1.3%, and HF in 2.4% vs. 2.7% (combination vs. monotherapy). Kaplan-Meier survival probabilities favored combination therapy: mortality, 94.71% vs. 88.74%; HF, 86.78% vs. 84.35%; MI, 91.46% vs. 91.62%; and stroke, 93.99% vs. 94.58%. Hazard ratios consistently favored combination therapy mortality HR 0.863 (0.732–1.017), MI HR 0.928 (0.775–1.112), stroke HR 0.966 (0.800–1.166), HF HR 0.901 (0.789–1.028) though none reached statistical significance. HF risk difference trended toward significance (p=0.071). Conclusion: Combination GLP-1 RA + SGLT2i therapy showed a consistent trend toward reduced MACE and mortality versus GLP-1 RA monotherapy in patients with fatty liver change, without reaching statistical significance. HF was the most frequent adverse outcome, underscoring the substantial cardiovascular burden in this population. Prospective randomized trials are warranted to confirm whether dual therapy offers superior cardiovascular protection in this high-risk group. Keywords Fatty change of liver · K76.0 · GLP-1 RA · SGLT2 inhibitor · MACE · Heart failure · Propensity score matching · TriNetX · Real-world evidence