P0925 - Glucagon-Like Peptide-1 Receptor Agonist and Pioglitazone Therapy Have Superior Mortality and Liver Outcomes for Patients With Type 2 Diabetes and a Diagnosis or at Risk for Undiagnosed Non-alcoholic Fatty Liver Disease

Benjamin D. Liu, MD¹, Mohamed Aly, BSc², Cindy Hsin-Ti Lin, MD³, Noordeep K.. Panesar, MS, MD⁴, Kamran Qureshi, MD^5
1MetroHealth, Cleveland, OH; ²Schulich School of Medicine and Dentistry, London, ON, Canada; ³MetroHeath Medical Center, Cleveland, OH; ⁴MetroHealth Medical Center, Cleveland, OH; ⁵Saint Louis University, St. Louis, MO

Introduction: Antidiabetic therapies Pioglitazone (PGZ) and Glucagon-Like Peptide-1 receptor Agonists (GLP1A) may have potential benefit in Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH). We evaluated the efficacy of these agents in Type 2 Diabetes (T2DM) patients with NAFLD/NASH in reducing all-cause mortality and adverse liver outcomes.

Methods: We queried TriNetX, a healthcare database that provides up to 20 years of de-identified aggregate data for over 123 million patients from 14 different countries. Patients were selected based on ICD-10 codes, with all patients having T2DM and either NAFLD or NASH, or a high risk of undiagnosed NAFLD/NASH (RISK) based on age > 50, ALT > 30, and T2DM. Patients could not have or be at risk for other chronic liver diseases or have a baseline high risk of mortality, according to the Charlson-Morbidity Index. We constructed 3 exclusive cohorts based on index event medication: Group 1 (GLP1A), Group 2 (PGZ), and Group 3 (other second-line T2DM medications). We matched Group 1 or Group 2 patients with Group 3 patients that had similar propensity scores on demographics, factors affecting the choice of second line T2DM medication, and factors predicting adverse liver outcomes. Matched patients were followed on an intention-to-treat basis for up to 20 years after medication initiation. Time-to-event analyses were performed using Kaplan-Meier analysis and Hazard ratios (HR) were estimated using Cox-proportional HR models with a p-value < 0.05 considered significant. The potential for unmeasured confounding was evaluated by E-value sensitivity analysis. We performed a sub-analysis on patients with an established diagnosis of cirrhosis.

Results: All-cause mortality was noted to be lower among both Group 1 (HR 0.58; 95% CI 0.55 – 0.61) and Group 2 (HR 0.92; 95% CI 0.85 – 0.99) when compared to Group 3. A similar reduction was noted in Group 1 when cirrhotic patients were compared (HR 0.61; 95% CI 0.52 – 0.71). Incidence rates of liver decompensation and HCC were reduced in both Group 1 and 2 when compared with Group 3. Reduction in Liver Transplant was noted only in Group 1 (HR 0.62; 95% CI 0.44 – 0.87). E-value analyses suggested unmeasured confounders were unlikely to change any outcome associations.

Discussion: In a real-world long-term study using a large database, the use of GLP1A and PGZ for T2DM management in NAFLD/NASH population was associated with reduced overall mortality and incidence of hepatic decompensation and HCC.




Disclosures:


Benjamin D. Liu, MD¹, Mohamed Aly, BSc², Cindy Hsin-Ti Lin, MD³, Noordeep K.. Panesar, MS, MD⁴, Kamran Qureshi, MD⁵. P0925 - Glucagon-Like Peptide-1 Receptor Agonist and Pioglitazone Therapy Have Superior Mortality and Liver Outcomes for Patients With Type 2 Diabetes and a Diagnosis or at Risk for Undiagnosed Non-alcoholic Fatty Liver Disease, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.