Association of GLP1‐receptor agonist use with liver disease progression, major cardiovascular events, and mortality in people with hepatic steatosis and diabetes

Abstract Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease in the United States. MASLD can progress to liver cirrhosis and is associated with an increased risk of major acute cardiovascular events (MACE). This study aimed to examine the association of glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) use with liver disease progression, MACE, and death from any cause among people with hepatic steatosis. Materials and Methods This retrospective cohort study using national data from the Department of Veteran Affairs included people with non‐alcoholic hepatic steatosis who initiated either GLP1‐RA or dipeptidyl‐peptidase‐4 inhibitor (DPP4i) between 1 October 2005 and 30 September 2021. Primary outcomes were: (1) liver disease progression and (2) MACE and death from any cause (MACE/death). GLP1‐RA users and DPP4i users were propensity score matched on 73 baseline characteristics. Results We matched 58 157 pairs of GLP1‐RA and DPP4i users. GLP1‐RA users had less liver disease progression (6.1%) compared with DPP4i users (7.0%), odds ratio (OR): 0.86; 95% confidence interval (95% CI): 0.82–0.90 and a lower risk of MACE/death (11.1% vs. 14.7%, respectively), OR: 0.72; 95% CI: 0.70–0.75. The number needed to treat to prevent one additional liver disease progression and MACE/death was 109 and 27 people, respectively. Conclusions Among people with diabetes and hepatic steatosis, GLP1‐RA use was associated with a lower risk of liver disease progression and a lower risk of MACE/death compared to DPP4i use. In people with MASLD, a holistic approach that seeks to lower MACE/death, beyond lowering liver disease progression alone, should be prioritised.