GLP-1-based treatments and long-term clinical outcomes in MASLD amongst older adults: a retrospective cohort study.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in older adults, driving hepatic decompensation and cardiovascular mortality. Randomised trial data on glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) therapy remain limited. METHODS: We conducted a retrospective cohort study using TriNetX US Collaborative Network. Adults 65 years or older with MASLD were identified by codes for fatty liver disease or steatohepatitis plus one cardiometabolic risk factor. We excluded liver transplant and other liver disease causes. Using a new-user, intention-to-treat design with 1:1 propensity-score matching, we compared GLP-1 RA initiators with unexposed patients. Outcomes were hepatic decompensation, hospitalisation, mortality and major adverse cardiovascular events (MACE), assessed 90 days to 10 years after index. Sensitivity analyses restricted follow-up to 1-10 years, excluded tirzepatide or began follow-up on day 1. FINDINGS: We identified 44 196 GLP-1 RA initiators and 384 672 unexposed patients. After matching, 43 930 remained per cohort (mean age 71.8 years; 62.0% female), with standardised mean differences below 0.1. GLP-1 RA use was linked to lower hazards of hepatic decompensation (hazard ratios [HR] 0.72, 95% confidence intervals [CI] 0.66-0.79), mortality (HR 0.55, 0.52-0.58) and hospitalisation (HR 0.95, 0.93-0.97). MACE showed no reduction (HR 0.98, 0.92-1.04). Osteoporosis without fracture and retinopathy were more frequent; pancreatitis, sarcopenia and fracture did not differ. GI events occurred more often as first events. Sensitivity analyses confirmed results for decompensation, hospitalisation and mortality. INTERPRETATION: In older adults with MASLD, GLP-1 RA initiation was linked to lower risks of hepatic decompensation, hospitalisation and mortality, with higher rates of selected adverse events.