Glucagon-like peptide-1 receptor agonists and incident cardiovascular events and death in treated serious mental illness, type 2 diabetes, and obesity

Authors

• Samuel B. Governor, St. John's Episcopal Hospital New York NY USA.
• David M. Dávila-García, Institute for Informatics, Data Science and Biostatistics Washington University School of Medicine St. Louis MO USA.
• Eliut Rivera-Segarra, School of Behavioral and Brain Sciences Ponce Health Sciences University Ponce PR USA.
• Lindsey M. Filiatreau, Bursky School of Public Health Washington University in St. Louis St. Louis MO USA.
• Nelmit Tollinchi-Natali, School of Dental Medicine Ponce Health Sciences University Ponce PR USA.
• Ekow Essien, Advocate Health - MidwestFollow
• Osamah Altaee, University of Texas Health San Antonio TX USA.
• Prince Otchere, University of Texas Health San Antonio TX USA.
• Leopoldo J. Cabassa, Brown School of Social Work and Center for Mental Health Services Research Washington University in St. Louis MO USA.
• Victor G. Dávila-Román, Cardiovascular Division and Global Health Center, Department of Medicine, School of Medicine and Bursky School of Public Health Washington University in St. Louis MO USA.

Recommended Citation

Governor SB, Dávila-García DM, Rivera-Segarra E, et al. Glucagon-Like Peptide-1 Receptor Agonists and Incident Cardiovascular Events and Death in Treated Serious Mental Illness, Type 2 Diabetes, and Obesity. J Am Heart Assoc. 2026;15(20):e051982. doi:10.1161/JAHA.126.051982

Affiliations

Aurora Health Care Kenosha

Abstract

Background: Adults with serious mental illness (SMI), type 2 diabetes, and obesity have elevated cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have established cardiometabolic benefits in the general population, but their effects in SMI are unclear. We evaluated whether GLP-1RA use was associated with lower risks of incident myocardial infarction (MI), heart failure (HF), and all-cause death.

Methods: This was a retrospective propensity score-matched cohort study of 218 043 adults with SMI, type 2 diabetes, obesity, and active antipsychotic or antidepressant medications in the TriNetX database (73 health care organizations). Outcomes were incident MI, HF, and all-cause death at 1 and 3 years. The primary exposure was GLP-1RA use versus nonuse; secondary analyses examined semaglutide or tirzepatide. Exploratory analyses evaluated sex, race, and sodium-glucose cotransporter-2 inhibitor and dipeptidyl peptidase-4 inhibitor use.

Results: GLP-1RA use was associated with lower risks of incident MI, HF, and all-cause death. Risk differences at 1 and 3 years were -0.007 and -0.010 for MI, -0.011 and -0.018 for HF, and -0.039 and -0.065 for death (all P<0.001). Semaglutide or tirzepatide use was also associated with lower risks of MI, HF, and death (all P<0.001). Findings were directionally consistent after accounting for sodium-glucose cotransporter-2 inhibitor and dipeptidyl peptidase-4 inhibitor use.

Conclusions: Adults with treated SMI, type 2 diabetes, and obesity using GLP-1RAs, particularly semaglutide or tirzepatide, had significantly reduced 1- and 3-year risks of incident MI, HF, and all-cause death versus nonusers. These pooled associations should be interpreted in the context of SMI's clinical heterogeneity and the limitations of administrative case ascertainment.

Type

Article

PubMed ID

42885796