Effects of glucagon-like peptide-1 receptor agonists on renal function

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus. A number of case reports show an association of GLP-1 receptor agonists, mainly exenatide, with the development of acute kidney injury. The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function, their use in subjects with chronic renal failure and their possible association with acute kidney injury. Based on the current evidence, exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease. Liraglutide is not eliminated by renal or hepatic mechanisms, but it should be used with caution since there are only limited data in patients with renal or hepatic impairment. There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect. Additionally, there is evidence that GLP-1 receptor agonists influence water and electrolyte balance. These effects may represent new ways to improve or even prevent diabetic nephropathy.

Keywords: Glucagon-like peptide 1, Glucagon-like peptide 1 receptor agonists, Exenatide, Liraglutide, Kidney, Renal impairment, Diabetic nephropathy, Electrolytes

Core tip: Glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control in patients with type 2 diabetes mellitus. A number of case reports show an association of GLP-1 receptor agonists, mainly exenatide, with the development of acute kidney injury. Exenatide is eliminated by renal mechanisms, but liraglutide is not eliminated by renal or hepatic mechanisms. GLP-1 receptor agonists exert protective role in animal models of diabetic nephropathy. The effects of these drugs may represent new ways to improve or even prevent diabetic nephropathy, but their exact mechanism of action need to be elucidated.