Cardiovascular and kidney outcomes of GLP ‐1 receptor agonists in adults with obesity: A target trial emulation study
Year: 2025
Type: article
Study design: Observational Study
Abstract: AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiovascular and renal benefits in type 2 diabetes, but their real-world effects in individuals with obesity without diabetes are unclear. This study aimed to evaluate the cardiovascular and kidney outcomes of GLP-1RAs versus other anti-obesity medications (AOMs) in adults with obesity. MATERIALS AND METHODS: This target trial emulation used TriNetX electronic health records (July 2021-May 2025) to identify adults with obesity and no diabetes history who initiated GLP-1RAs (liraglutide, semaglutide, or tirzepatide) or other AOMs. Outcomes included major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), all-cause mortality, mental health conditions, and safety outcomes. Propensity score matching (1:1) balanced baseline characteristics; Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The study included 140 169 matched pairs of GLP-1RA and AOM initiators. Mean follow-up was 392 days for GLP-1RA users and 564 days for AOM users. Compared to AOMs, GLP-1RA use was associated with lower risks of MACE (HR, 0.76; 95% CI, 0.72-0.81), MAKE (HR, 0.64; 95% CI, 0.55-0.74), and all-cause mortality (HR, 0.49; 95% CI, 0.42-0.57). Mental health outcomes also improved, with reduced risks of depression (HR, 0.63), suicidal ideation/attempt (HR, 0.42), and substance use disorder (HR, 0.58). GLP-1RAs were not associated with increased risks of acute pancreatitis (HR, 1.17), hypoglycemia (HR, 1.08), or gastrointestinal symptoms (HR, 0.99). CONCLUSIONS: Among adults with obesity but without diabetes, GLP-1RA use was associated with reduced cardiovascular, kidney, mortality, and mental health risks compared to other AOMs.
Source: Diabetes Obesity and Metabolism
DOI: 10.1111/dom.70054
Authors: Huilin Tang, Yiwen Lu, Bingyu Zhang, Ting Zhou, Dazheng Zhang, Jiajie Chen, Yong Chen, Yong Chen, David A. Asch, Yong Chen, Yong Chen
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,380
Funders: National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Eye Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, U.S. National Library of Medicine, NIH Clinical Center, National Center for Advancing Translational Sciences
Awards: G1110151009, G1976838505, G263146048, G3337470798, G3681229956, Methods for Estimating Disease Burden of Seasonal Influenza, G5129465064, AI-ADRD: Accelerating interventions of AD/ADRD via Machine learning methods, G5422992166, G5648657692, G6776800937, G7414391159, Surrogate Augmented Deep Predictive Learning for Retinopathy of Prematurity, Coordinating Individually Measured Phenotypes to Advance Mental Health Research, G9000027382, G9000053926, Novel evidence-accumulation-driven methods for characterizing kidney stone progression, PANDA-MSD: Predictive Analytics via Networked Distributed Algorithms for Multi-System Diseases, TRiPOD: Toward Reusable Phenotypes in Observational Data for AD/ADRD - managing definitions and correcting bias
OpenAlex ID: W4413799578