The impact of the glucagon‐like peptide‐1 receptor agonist liraglutide on natriuretic peptides in heart failure patients with reduced ejection fraction with and without type 2 diabetes

Abstract Aim To assess the effect of liraglutide, a glucagon‐like peptide‐1 receptor agonist, on urinary sodium excretion as well as on circulating adrenomedullin and copeptin levels in patients with type 2 diabetes (T2D). Materials and methods In the LIVE study, patients (n = 241) with left ventricular ejection fraction ≤45% were randomized to liraglutide 1.8 mg daily or placebo for 24 weeks, and 30% had a concomitant diagnosis of T2D. Plasma levels of N‐terminal brain‐natriuretic‐peptide (NT‐proBNP) (a predefined secondary endpoint), midregional pro‐atrial‐natriuretic‐peptide (MR‐proANP), midregional pro‐adrenomedullin (MR‐proADM) and copeptin were measured at baseline and after 24 weeks in this substudy. The potential effect modification of T2D was assessed. Results In the eligible subgroup of 231 patients with available biomarkers (115 randomized to liraglutide and 116 to placebo), MR‐proANP decreased by 12% ( P = .002) and NT‐proBNP by 9% ( P = .009) during liraglutide treatment compared with placebo at week 24. Interaction with T2D for the treatment effect of change in MR‐proANP and NT‐proBNP levels was P = .003 and P = .03, respectively. Consequently, in patients with T2D, liraglutide decreased MR‐proANP by 27% ( P < .001) and NT‐proBNP by 25% ( P = .02) compared with placebo, whereas no change was observed in patients without T2D. There was no effect of liraglutide on MR‐proADM ( P = .10) or copeptin ( P = .52). Conclusion Liraglutide decreased the A‐ and B‐type natriuretic peptides significantly in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant T2D, suggesting a beneficial mechanism of liraglutide in T2D patients with HFrEF.