Diabetes, obesity & metabolism · 2026
Association of GLP-1 Receptor Agonists With Hepatic Decompensation in the All of Us Research Program.
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Hwang Inyoung, Kim Yun, Lee Sang Won
Аннотация
AIMS: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) initiation and the risk of hepatic decompensation compared with dipeptidyl peptidase 4 inhibitors (DPP4is) in a racially and ethnically diverse cohort of adults with Type 2 diabetes.
MATERIALS AND METHODS: This retrospective active-comparator new-user cohort study utilised data from the National Institutes of Health's All of Us Research Program. Adult participants with Type 2 diabetes initiating GLP-1RAs or DPP4is without prior hepatic decompensation or competing causes of chronic liver disease were identified. Stratified propensity score matching (1:1) was employed to balance baseline covariates. The primary outcome was a composite of hepatic decompensation events (oesophageal varices with bleeding, ascites, hepatic encephalopathy, hepatic failure, or liver transplantation). Hazard ratios (HRs) were estimated using Cox proportional hazards regression.
RESULTS: The matched cohort included 7854 participants (mean age 57.3 years; 58.8% female; 24.8% Black or African American). GLP-1RA use was associated with a significantly reduced risk of hepatic decompensation compared with DPP4i use (HR 0.67; 95% CI 0.47-0.95; p = 0.026), corresponding to an absolute rate difference of -1.66 events per 1000 person-years. Estimates were directionally similar in prespecified sensitivity analyses.
CONCLUSIONS: In this diverse nationwide cohort, initiation of GLP-1RAs was associated with a significantly reduced risk of hepatic decompensation compared with DPP4is. These findings extend prior evidence by demonstrating this association in a cohort enriched for populations historically underrepresented in biomedical research.
MATERIALS AND METHODS: This retrospective active-comparator new-user cohort study utilised data from the National Institutes of Health's All of Us Research Program. Adult participants with Type 2 diabetes initiating GLP-1RAs or DPP4is without prior hepatic decompensation or competing causes of chronic liver disease were identified. Stratified propensity score matching (1:1) was employed to balance baseline covariates. The primary outcome was a composite of hepatic decompensation events (oesophageal varices with bleeding, ascites, hepatic encephalopathy, hepatic failure, or liver transplantation). Hazard ratios (HRs) were estimated using Cox proportional hazards regression.
RESULTS: The matched cohort included 7854 participants (mean age 57.3 years; 58.8% female; 24.8% Black or African American). GLP-1RA use was associated with a significantly reduced risk of hepatic decompensation compared with DPP4i use (HR 0.67; 95% CI 0.47-0.95; p = 0.026), corresponding to an absolute rate difference of -1.66 events per 1000 person-years. Estimates were directionally similar in prespecified sensitivity analyses.
CONCLUSIONS: In this diverse nationwide cohort, initiation of GLP-1RAs was associated with a significantly reduced risk of hepatic decompensation compared with DPP4is. These findings extend prior evidence by demonstrating this association in a cohort enriched for populations historically underrepresented in biomedical research.