The Incretin System: Glucagon-Like peptide-1 Receptor Agonists and Dipeptidyl peptidase-4 Inhibitors in Type 2 Diabetes

Lancet. 2006 Nov 11;368(9548):1696-705. doi: 10.1016/S0140-6736(06)69705-5.

Abstract

Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Adenosine Deaminase Inhibitors*
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Drug Administration Schedule
  • Exenatide
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / biosynthesis
  • Glucagon-Like Peptide 1 / classification
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor
  • Glycoproteins / antagonists & inhibitors*
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Liraglutide
  • Nitriles
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Pyrrolidines
  • Receptors, Glucagon / agonists*
  • Sitagliptin Phosphate
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*
  • Venoms / administration & dosage
  • Venoms / adverse effects
  • Venoms / therapeutic use*
  • Vildagliptin

Substances

  • Adenosine Deaminase Inhibitors
  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycoproteins
  • Hypoglycemic Agents
  • Nitriles
  • Peptides
  • Pyrazines
  • Pyrrolidines
  • Receptors, Glucagon
  • Triazoles
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Vildagliptin
  • Adamantane
  • Sitagliptin Phosphate