Mechanisms and clinical applications of incretin therapies for diabetes and chronic kidney disease

Curr Opin Nephrol Hypertens. 2023 Jul 1;32(4):377-385. doi: 10.1097/MNH.0000000000000894. Epub 2023 May 4.

Abstract

Purpose of review: Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. Development of DKD increases risks for cardiovascular events and death. Glucagon-like peptide-1 (GLP-1) receptor agonist have demonstrated improved cardiovascular and kidney outcomes in large-scale clinical trials.

Recent finding: GLP-1 and dual GLP-1/glucose-depending insulinotropic polypeptide (GIP) receptor agonists have robust glucose-lowering efficacy with low risk of hypoglycemia even in advanced stages of DKD. Initially approved as antihyperglycemic therapies, these agents also reduce blood pressure and body weight. Cardiovascular outcome and glycemic lowering trials have reported decreased risks of development and progression of DKD and atherosclerotic cardiovascular events for GLP-1 receptor agonists. Kidney and cardiovascular protection is mediated partly, but not entirely, by lowering of glycemia, body weight, and blood pressure. Experimental data have identified modulation of the innate immune response as a biologically plausible mechanism underpinning kidney and cardiovascular effects.

Summary: An influx of incretin-based therapies has changed the landscape of DKD treatment. GLP-1 receptor agonist use is endorsed by all major guideline forming organizations. Ongoing clinical trials and mechanistic studies with GLP-1 and dual GLP-1/GIP receptor agonists will further define the roles and pathways for these agents in the treatment of DKD.

Publication types

  • Review

MeSH terms

  • Body Weight
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Glucose / therapeutic use
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Incretins / adverse effects
  • Renal Insufficiency, Chronic* / drug therapy

Substances

  • Incretins
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1
  • Glucose
  • Glucagon-Like Peptide-1 Receptor Agonists