GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes

Nat Rev Nephrol. 2017 Oct;13(10):605-628. doi: 10.1038/nrneph.2017.123. Epub 2017 Sep 4.

Abstract

The gastrointestinal tract - the largest endocrine network in human physiology - orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies - GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors - for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut-renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut-renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.

Publication types

  • Review

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / physiopathology
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Glucagon-Like Peptide 1 / physiology*
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism*
  • Hyperglycemia / physiopathology
  • Hypoglycemic Agents / pharmacology*
  • Incretins / pharmacology*
  • Risk Factors

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Incretins
  • Glucagon-Like Peptide 1