Hemodynamic effect of a single dose of glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide in patients with diabetic kidney disease.

Increased peripheral resistance and autonomic nervous system is a key link in pathogenesis of arterial hypertension in diabetic kidney disease. Net effect of glucagon-like peptide 1 receptor (GLP-1R) agonists on blood pressure may result from interplay between vasodilatation, increased natriuresis, heart rate and sympathetic nervous system activity. The aim of study was to compare hemodynamic effect of single subcutaneous dose of 1.2 mg liraglutide to placebo in patients with type 2 diabetes mellitus and impaired renal function. This cross-over study included 17 patients with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m and 17 patients with eGFR > 60 ml/min/1.73 m. Blood pressure and heart rate were monitored for 24 hours after liraglutide or placebo. Before and after each medication, systemic vascular resistance, heart rate variability, pulse wave velocity and central blood pressure were measured. Significant increases of 24 h mean heart rate and cardiac output were seen in both groups. Sympathetic predominance was observed in patients with eGFR < 30 ml/min/1.73 m after GLP-1R agonist compared to placebo (p = 0.005). Systemic vascular resistance decreased after liraglutide compared with placebo only in patients with eGFR > 60 ml/min/1.73 m (p = 0.002), whereas pulse wave velocity increased after liraglutide compared with placebo only in patients with eGFR < 30 ml/min/1.73 m (p = 0.0006). The 24 h mean arterial pressure after liraglutide significantly increased compared to placebo only in latter group. Liraglutide administration in patients with advanced chronic kidney disease (CKD) induces increase of blood pressure due to increase of cardiac output secondary to acceleration of heart rate associated with sympathetic predominance. The vasodilatory effect of liraglutide is preserved only in earlier CKD.