Effect of Glucagon-like Peptide-1 Receptor Agonists on Prognosis of Heart Failure and Cardiac Function: A Systematic Review and Meta-analysis of Randomized Controlled Trials

PURPOSE: Whether an antidiabetic drug, glucagon-like peptide-1 receptor agonist (GLP-1RA), could improve the prognosis of heart failure and cardiac function remains controversial. We conducted a systematic review and meta-analysis of randomized controlled trials to explore the influence of GLP-1RAs on heart failure in patients regardless of diabetes diagnosis. METHODS: Literature in English from the PubMed, EMBASE, and Cochrane Library databases was searched from inception to July 2022. The study aim was to identify published, randomized, placebo-controlled trials testing GLP-1RAs in patients with or without diabetes. Outcomes were heart failure hospitalization, cardiac function, and structure measures. FINDINGS: Twenty-two randomized controlled trials involving 61,412 patients are included in the meta-analysis. Overall, compared with the placebo group, GLP-1RA treatment could not significantly decrease heart failure hospitalization in patients with a history of heart failure (hazard ratio [HR], 1.07; 95% CI, 0.91 to 1.25; P = 0.422). Six-minute walking test distances (WMD, 19.08 m; 95% CI, 4.81 to 33.36; P = 0.01), E-wave (SMD, -0.40; 95% CI, -0.60 to -0.20; P < 0.001), early diastolic to late diastolic velocities ratio (WMD, -0.10; 95% CI, -0.18 to -0.02; P = 0.01), mitral inflow E velocity to tissue Doppler e' ratio (WMD, -0.97; 95% CI, -1.54 to -0.41; P < 0.001), and E-wave deceleration time (WMD, -9.96 milliseconds; 95% CI, -18.52 to -1.41; P = 0.02) increased significantly after administration of GLP-1RAs. However, GLP-1RAs do not significantly influence N-terminal pro-B-type natriuretic peptide levels (WMD, -20.02 pg/mL; 95% CI, -53.12 to 13.08; P = 0.24), Minnesota Living with Heart Failure Questionnaire quality of life scores (WMD, -1.08; 95% CI, -3.99 to 1.84; P = 0.47), or left ventricular ejection fractions (WMD, -0.37%; 95% CI, -1.19 to 0.46; P = 0.38). IMPLICATIONS: GLP-1RAs did not reduce heart failure readmissions in patients with a history of heart failure and elevated N-terminal pro-B-type natriuretic peptide levels. Thus, the prognosis of heart failure was not improved, although GLP-1RAs did significantly improve left ventricular diastolic function in patients. PROSPERO identifier: CRD42021226231.