Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial

Aims: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. Methods: The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included Cr-51-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. Results: Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2)] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. Conclusions: Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.