Real-world comparison of GLP-1 agonists versus physical activity in metabolic dysfunction-associated steatotic liver disease

Glucagon-like peptide-1 (GLP-1) receptor agonists have metabolic and hepatic benefits in metabolic dysfunction–associated steatotic liver disease (MASLD), but their additive benefit compared to lifestyle modification only in real-world settings remains uncertain. This study compared the effects of GLP-1 agonist therapy and physical activity on body mass index (BMI) and noninvasive liver metrics in a predominantly Hispanic clinical population with MASLD. This is a retrospective longitudinal study of 202 adults with MASLD evaluated at an outpatient gastroenterology clinic. BMI, controlled attenuation parameter (CAP), liver stiffness (kPa), and Fibrosis-4 (FIB-4) indices were analyzed at baseline and follow-up (1–2 years). Primary analyses compared follow up outcomes between GLP-1 therapy and an unmonitored physical activity comparator group; exploratory analyses assessed whether effects differed by sex or ethnicity. Among 193 patients with complete BMI data and 131 with liver metrics, GLP-1 agonist therapy was associated with a greater reduction in BMI (–1.47 kg/m²; 95% CI, − 2.54 to − 0.41; p = 0.007) and in FIB-4 indices (–0.29; 95% CI, − 0.56 to − 0.03; p = 0.029) compared with physical activity only. Adjusted differences in CAP (–3.31 dB/m) and liver stiffness (+ 0.01 kPa) were not statistically significant. In this real-world MASLD cohort, GLP-1 therapy was associated with greater baseline-adjusted improvements in BMI and FIB-4 compared with physical activity alone, while CAP and liver stiffness were not statistically significant. These findings provide supportive real-world evidence for GLP-1 associated metabolic benefit and warrant confirmation of hepatic effects in larger prospective studies, including cohorts with substantial Hispanic representation.