67 - Dual Therapy With Metformin and Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) Improves Mortality in Diabetic Cirrhotic Patients

Daniel J. Huynh, BS¹, Benjamin D. Renelus, MD², Daniel S. Jamorabo, MD^3
1Renaissance School of Medicine, Stony Brook, NY; ²Morehouse School of Medicine, Atlanta, GA; ³Stony Brook Medicine, Stony Brook, NY

Introduction: Diabetes mellitus (DM) is a common comorbidity of cirrhosis, but there is limited research on the impact of dual diabetes therapies on mortality and hepatic decompensation in cirrhosis, particularly in non-alcoholic fatty liver disease (NAFLD).

Methods: We carried out propensity score-matched analyses of DM patients with cirrhosis comparing those on metformin with those on both metformin and an GLP1-RA. We queried for people with both Type 2 DM (DM2) and cirrhosis using ICD-10 codes on the TriNetX network. We collected patient demographics—age, sex, race, among others—and our primary outcome was mortality in three years. Our secondary outcome was a composite of hepatic decompensation events—hepatic encephalopathy, ascites, and variceal bleeding—over three years.

Results: We identified 873 patients with cirrhosis and DM2 who were on both metformin and a GLP1-RA. This cohort included 592 Whites (67.8%), 499 women (57.2%), had a mean age of 60.9 years, and was matched with a baseline group of patients who were on metformin alone (Table 1). The monotherapy group had a greater mortality risk (RR 2.2, 95%CI 1.5-3.2, p< 0.0001) with survival probability 83.3% at 3 years compared to the dual therapy group (93.6%, p< 0.0001). We also identified a subset of 204 patients within the dual therapy group that was confirmed to have cirrhosis from non-alcoholic steatohepatitis (NASH) and that included 157 Whites (77.0%), 142 women (69.6%), and had a mean age of 58.9 years. When comparing the NASH cohorts, they had equivalent mortality risk (RR 1.0, 95%CI 0.4-2.4, p=1) and survival at 3 years (95.5% vs. 97.8%, p=0.05). The composite risk for hepatic decompensation was equivalent between both therapy groups (Figure 1).

Discussion: We found a potential mortality benefit in cirrhosis patients on dual metformin and GLP1-RA compared to metformin alone that was durable over a 3-years though this did not persist in our NASH subset. This finding was consistent for men, women, and White patients but particularly more pronounced in older men in our matched cohort analyses. There were too few non-White patients in the NASH cohort for meaningful analysis. Further, there was no clear effect on the composite risk for hepatic decompensation, and the lack of mortality benefit may be due to underreporting of NASH ICD-10 codes in the database. Further prospective studies in patients with biopsy-confirmed NASH and especially from underrepresented populations are needed to investigate our primary and secondary outcomes.




Disclosures:


Daniel J. Huynh, BS¹, Benjamin D. Renelus, MD², Daniel S. Jamorabo, MD³, 67, Dual Therapy With Metformin and Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) Improves Mortality in Diabetic Cirrhotic Patients, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.