P1544 - Real-World Benefits of GLP-1RA Therapy in MASLD: Reductions in Cardiovascular, Renal, Hepatic, and Mortality Outcomes

Sana Rabeeah, MD¹, Mohammed Abu-Rumaileh, MD¹, Bisher Sawaf, MD², Yusuf Omar Hallak, MD¹, Maram Albandak, MD¹, Sudheer Dhoop, MD³, Muhamad Hijazi, MD⁴, Sami Ghazaleh, MD³, Monica Tincopa, MD⁵
1The University of Toledo, Toledo, OH; 2University of Toledo Medical Center, Toledo, OH; 3University of Toledo, Toledo, OH; 4TriHealth, Cincinnati, OH; 5UCSD, San Diego, CA

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to adverse cardiovascular, renal, and hepatic outcomes. GLP-1 receptor agonists (GLP-1RAs), such as semaglutide, dulaglutide, and tirzepatide, offer metabolic and anti-inflammatory effects that may mitigate disease progression. This study aimed to evaluate the association between GLP-1RA use and clinical outcomes in individuals with MASLD using a large population-based cohort.

Methods: Adults with MASLD were identified from the TriNetX Global Network. Individuals with alcohol-related liver disease, type 1 diabetes, or liver transplant were excluded. GLP-1RA exposure was defined by prescription of semaglutide, dulaglutide, or tirzepatide. Patients were matched 1:1 using propensity scores based on demographics, comorbidities, and baseline labs. Primary outcomes included cardiovascular events, renal complications, liver-related outcomes, and mortality over a follow-up of up to 5 years.

Results: After propensity matching, 211,640 patients were included in each group. GLP-1RA use was associated with significantly lower hazards for several outcomes: cardiac arrest (HR 0.51, 95% CI 0.45–0.58), myocardial infarction (HR 0.87, 95% CI 0.82–0.92), ischemic stroke (HR 0.86, 95% CI 0.80–0.92), and heart failure (HR 0.84, 95% CI 0.80–0.88), all p< 0.001. Renal outcomes were also improved, with reduced hazards for dialysis (HR 0.64, 95% CI 0.57–0.72) and progression to advanced CKD (HR 0.77, 95% CI 0.73–0.82), both p< 0.001. Hepatic complications were significantly reduced for ascites (HR 0.56, 95% CI 0.51–0.62) and spontaneous bacterial peritonitis (HR 0.43, 95% CI 0.30–0.62), but not for cirrhosis (HR 0.97, 95% CI 0.92–1.02), variceal bleeding (HR 0.90, 95% CI 0.75–1.09), or portal hypertension (HR 0.94, 95% CI 0.88–1.01). Elevated liver enzymes occurred less frequently (HR 0.58, 95% CI 0.54–0.63, p< 0.001), and all-cause mortality was substantially reduced (HR 0.39, 95% CI 0.37–0.42, p< 0.001).

Discussion: In this large, matched cohort of MASLD patients, GLP-1RA therapy was associated with reduced cardiovascular, renal, and hepatic complications and lower mortality. These findings support further prospective trials evaluating GLP-1RAs as potential disease-modifying agents in MASLD.

Disclosures:
Sana Rabeeah indicated no relevant financial relationships.
Mohammed Abu-Rumaileh indicated no relevant financial relationships.
Bisher Sawaf indicated no relevant financial relationships.
Yusuf Omar Hallak indicated no relevant financial relationships.
Maram Albandak indicated no relevant financial relationships.
Sudheer Dhoop indicated no relevant financial relationships.
Muhamad Hijazi indicated no relevant financial relationships.
Sami Ghazaleh indicated no relevant financial relationships.
Monica Tincopa indicated no relevant financial relationships.

Sana Rabeeah, MD¹, Mohammed Abu-Rumaileh, MD¹, Bisher Sawaf, MD², Yusuf Omar Hallak, MD¹, Maram Albandak, MD¹, Sudheer Dhoop, MD³, Muhamad Hijazi, MD⁴, Sami Ghazaleh, MD³, Monica Tincopa, MD⁵. P1544 - Real-World Benefits of GLP-1RA Therapy in MASLD: Reductions in Cardiovascular, Renal, Hepatic, and Mortality Outcomes, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.