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

Abstract

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. 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. 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). 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.