Glucagon-like Peptide-1 Receptor Agonists Are Associated With Improved Survival and Reduced Liver-Related Events in Patients With Type 2 Diabetes and Metabolic Dysfunction-Associated Liver Disease: A Large Real-World Retrospective Study

Apr 30, 2025Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

Glucagon-like Peptide-1 Treatments Linked to Better Survival and Fewer Liver Problems in Type 2 Diabetes with Metabolic Liver Disease

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Abstract

GLP-1 receptor agonists are associated with a 40.9% reduction in all-cause mortality in patients with type 2 diabetes and liver disease.

GLP-1 receptor agonists were linked to a 40.9% reduction in all-cause mortality compared to controls.
Patients receiving GLP-1 receptor agonists had significantly lower rates of liver-related outcomes, including a 23% reduction in events leading to liver transplantation.
Pioglitazone was associated with a 32% reduction in liver-related outcomes but did not affect mortality rates.
In patients with cirrhosis, GLP-1 receptor agonists were associated with fewer transplant events, although they did not significantly reduce mortality.
GLP-1 receptor agonist therapy resulted in greater reductions in body mass index and hemoglobin A1c compared to controls.

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OBJECTIVES: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or pioglitazone (PGZ) are associated with improved survival, reduced liver-related outcomes (LROs), and better metabolic outcomes in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD) or steatohepatitis (MASH).

METHODS: We used the TriNetX platform to identify adults with T2DM and MASLD/MASH from 2006 onward (n = 558 075) using Internation Classification of Diseases codes. Patients with confounding liver diseases, overlapping study medications, or bariatric surgery were excluded. Three exclusive cohorts-GLP-1 RA, PGZ, and other antidiabetic agents (controls)-were formed. After 1:1 propensity score matching, time-to-event analyses were performed using Cox proportional hazards models and Kaplan-Meier methods.

RESULTS: Among matched groups, GLP-1 RAs (n = 17 465) were associated with a 40.9% reduction in all-cause mortality versus controls (hazard ratio [HR] 0.59; P < .0001) and significantly lower rates of LRO (HR 0.77) and liver transplantation (HR 0.33). In contrast, PGZ (n = 1803) showed reduced LRO rates (HR 0.68) but not mortality. In cirrhotic patients, GLP-1 RA was linked to fewer transplant events but did not significantly reduce mortality. GLP-1 RA therapy noted greater reductions in body mass index and hemoglobin A1c relative to controls.

CONCLUSIONS: In this large real-world cohort, GLP-1 RA use was associated with improved survival and hepatic outcomes in T2DM patients with MASLD/MASH, particularly among those without established cirrhosis. PGZ exhibited hepatic benefits. These findings highlight the potential importance of further prospective studies to evaluate early GLP-1 RA therapy in this high-risk diabetic population with MASLD/MASH.

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Glucagon-like Peptide-1 Receptor Agonists Are Associated With Improved Survival and Reduced Liver-Related Events in Patients With Type 2 Diabetes and Metabolic Dysfunction-Associated Liver Disease: A Large Real-World Retrospective Study

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