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

Diabetes Obes Metab. 2016 Jun;18(6):581-9. doi: 10.1111/dom.12651. Epub 2016 Mar 22.

Abstract

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 (51) Cr-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.

Keywords: atrial natriuretic peptide; catecholamines; glomerular filtration rate; glucagon-like peptide-1; liraglutide; renal; renin-angiotensin system; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin II / blood*
  • Atrial Natriuretic Factor / blood*
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Heart Rate / drug effects
  • Humans
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / physiology
  • Kidney Function Tests
  • Liraglutide / pharmacology*
  • Male
  • Middle Aged
  • Placebos
  • Renal Circulation / drug effects
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology

Substances

  • Placebos
  • Angiotensin II
  • Liraglutide
  • Atrial Natriuretic Factor