Glucagon-like Peptide-1 Receptor Agonists Improve Liver and Metabolic Health Outcomes in Type 2 Diabetes and Obesity Regardless of Prior Liver Disease

Metabolic dysfunction- associated steatotic liver disease (MASLD) is a common comorbidity in obesity and type 2 diabetes mellitus (T2DM), which are treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA). The benefits of GLP-1 RA on major adverse liver outcomes (MALO) in this population are not well established. We retrospectively evaluated the impact of GLP-1 RA, compared to propensity-matched controls, on mortality, MALO, major adverse cardiac events (MACE), and obesity- related cancers in obese adults with T2DM using the Tri NetX global collaborative database. GLP-1 RA decreased all-cause mortality (1.7 vs 5.4% H.R. (95% CI) 0.38, 0.37–0.39 at 2 years), MACE (4.4 vs 8.2% H.R. 0.66, 0.65–0.68), MALO (0.7 vs 1.8% H.R. 0.5, 0.49–0.55) and obesity-related cancers (1.5 vs 2.2%, H.R. 0.85, 0.81–0.89) and at all durations of exposure studied. GLP-1 RA improved the rates of each of the MACE components (p < 0.0001 for each). GLP-1 RA reduced ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular cancer (p < 0.01 for all outcomes). These benefits were confirmed in those who also had a diagnosis of either MASLD or cirrhosis prior to the initiation of GLP-1 RA. These data demonstrate the liver and metabolic health benefits of GLP-RAs and support access to these agents. Word count 199