GLP-1 RAs Linked to Lower Risk of Hepatic Complications in MASLD and T2D
Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with significantly lower rates of hepatic complications among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM), according to a large real-world cohort study.
Although randomized clinical trials have demonstrated that GLP-1 RAs improve histologic endpoints in steatotic liver disease, their impact on long-term liver outcomes has remained uncertain. To address this question, investigators analyzed data from the All of Us Research Program between 2010 and 2023 using a retrospective, new-user cohort design that emulated sequential monthly target trials.
The study included 2110 GLP-1 RA users matched to 2110 nonusers with MASLD and T2DM. Participants with prior hepatic complications or other chronic liver diseases were excluded. The primary outcome was a composite of incident cirrhosis, hepatic decompensation, hepatocellular carcinoma, or liver transplantation.
Over a median follow-up of 2.7 years, investigators observed 187 hepatic complication events. Seventy-four events occurred among GLP-1 RA users, corresponding to 13.5 events per 1000 person-years, compared with 113 events among nonusers, or 21.9 events per 1000 person-years.
GLP-1 RA therapy was associated with significantly lower risk of hepatic complications in both primary analyses. In the intention-to-treat analysis, use of a GLP-1 RA was associated with a “38% lower risk” of hepatic complications (hazard ratio [HR], 0.62; 95% CI, 0.46–0.83; P = .003). Results were similar in the per-protocol analysis, which demonstrated a “42% lower risk” (HR, 0.58; 95% CI, 0.42–0.80; P = .001).
Subgroup analyses based on baseline FIB-4 scores and body mass index showed consistent directional findings. Landmark analyses conducted at 6 months also supported the primary results. Investigators additionally reported no association between GLP-1 RA use and the negative control outcome of incident fracture.
Reference
Almazan, Erik, Choi, Jonggi, Kamath, Tushar, et al. GLP-1 receptor agonist use and liver-related outcomes in MASLD and type 2 diabetes in the All of Us Research Program. The American Journal of Gastroenterology ():10.14309/ajg.0000000000004048, May 12, 2026. | DOI: 10.14309/ajg.0000000000004048
