A. Sidney Barritt, MD: Real-World Data Suggest Benefit of GLP-1 RAs for MASLD

New research is providing clinicians with an overview of the characteristics and disease progression of patients with metabolic dysfunction associated steatotic liver disease (MASLD) who were prescribed GLP-1 RAs in real-world settings.

Findings from the analysis of the TARGET-NASH cohort were presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California, by A. Sidney Barritt, MD, a professor at the University of North Carolina and director of hepatology at the University of North Carolina Liver Center, and suggest use of these agents is associated with a reduced risk of all-cause mortality and progression from compensated to decompensated MASH cirrhosis.

“GLP-1 receptor agonists are already FDA-approved for use in diabetes and for obesity. As these are the 2 main risk factors for MASLD and MASH, we're already using these drugs in patients with MASLD and MASH,” Barritt explained to HCPLive. “These medications have already been in play in this patient population, so one of the reasons why we did the study that we did is to look and see if these medications actually impact hard measurable outcomes that patients are interested in.”

Among 6603 TARGET-NASH participants, 4219 met analysis criteria for MASL (n = 1311), MASH (n = 1331), and MASH cirrhosis (n = 1577), 375 of whom were GLP-1 RA users. Investigators noted GLP-1 RA users more commonly had type 2 diabetes, were enrolled at an endocrinology site, and had greater BMI relative to GLP-1 RA non-users (all P <.001).

Overall, 20 (5%) GLP-1 RA users died and 33 (20%) progressed from compensated to decompensated cirrhosis vs 243 (6%) and 217 (23%) non-users, respectively, and the median times to decompensation were 24.2 and 21.2 months. Adjusted hazard ratios (HR) indicated higher risk for all-cause mortality and progression from compensated to decompensated cirrhosis for GLP-1 RA non-users compared to users (HR, 2.28; 95% CI, 1.43-3.60 vs HR, 1.69; 95% CI, 1.16-2.46).

Investigators pointed out participants with type 2 diabetes, hypertension, and those who were >60 years of age had a greater risk of all-cause mortality than those without these risk factors, and those with hypertension were at a greater risk of progression to decompensation.

“What this research shows us is that in real-world clinical practice, number 1, we're already using these medications, and number 2, we have a signal here that they will influence these hard patient-important outcomes like symptomatic liver disease, decompensated liver disease, and mortality,” Barritt said.

References

1. ^{Barritt A, Mospan A, Munoz B, et al. Use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in patients with MASLD in a real-world setting is associated with slower disease progression and lower all-cause mortality. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
2. ^{Target RWE. TARGET-NASH. Accessed November 19, 2024. https://www.targetrwe.com/unique-data/registries/target-nash/}