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.