AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Diet Quality as an Unrecognized Effect Modifier of GLP-1 Receptor Agonist Cardiovascular Outcomes: A Systematic Review and Translational Framework
By Ravinuthala RP, Gyimah FT
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE), heart failure outcomes, and cardiovascular mortality in patients with type 2 diabetes and obesity. However, substantial inter-individual variability in cardiovascular response remains unexplained. Diet quality is a major determinant of cardiometabolic risk and incretin physiology and may represent an underrecognized modifier of GLP-1 RA cardiovascular efficacy. Objective: To evaluate whether existing clinical and mechanistic evidence supports diet quality as a potential effect modifier of GLP-1 receptor agonist cardiovascular outcomes and to identify critical evidence gaps relevant to precision cardiometabolic medicine. Methods: This systematic review was conducted in accordance with PRISMA guidelines and prospectively registered in PROSPERO (CRD420261372471). PubMed/MEDLINE and Scopus were searched from inception through April 2026. Eligible studies included randomized cardiovascular outcome trials, observational cohorts, dietary intervention studies, and mechanistic human studies evaluating GLP-1 RAs and/or dietary exposures relevant to cardiometabolic health. Primary outcomes included MACE, cardiovascular mortality, and heart failure hospitalization. A structured narrative synthesis integrating mechanistic, behavioral, and pharmacologic evidence was performed. Results: Eleven randomized and interventional studies were included, comprising GLP-1 RA cardiovascular outcome trials, dietary pattern cardiovascular research, and mechanistic investigations of incretin physiology. Evidence consistently demonstrated that dietary quality influences endogenous GLP-1 signaling through nutrient-mediated secretion, gut microbiome-derived metabolites, inflammatory pathways, and metabolic regulation. Dietary quality and GLP-1 RAs exerted convergent effects on major cardiometabolic risk pathways, including adiposity, insulin resistance, endothelial dysfunction, and systemic inflammation. Conclusions: Diet quality and GLP-1 receptor agonists converge on shared metabolic and inflammatory pathways that influence cardiovascular risk. Current evidence supports a biologically plausible interaction with potential implications for treatment response; however, clinical validation is lacking. Future cardiovascular outcome trials should incorporate dietary quality stratification to advance precision nutrition and precision cardiometabolic medicine.