Incretin hormone mimetics and analogues in diabetes therapeutics

Best Pract Res Clin Endocrinol Metab. 2007 Dec;21(4):497-516. doi: 10.1016/j.beem.2007.09.003.

Abstract

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are physiological gut peptides with insulin-releasing and extrapancreatic glucoregulatory actions. Incretin analogues/mimetics activate GLP-1 or GIP receptors whilst avoiding physiological inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the newest classes of antidiabetic drug. The first clinically approved GLP-1 mimetic for the treatment of type-2 diabetes is exenatide (Byetta/exendin) which is administered subcutaneously twice daily. Clinical trials of liraglutide, a GLP-1 analogue suitable for once-daily administration, are ongoing. A number of other incretin molecules are at earlier stages of development. This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. Additionally, it explores the therapeutic possibilities offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon hybrid peptides, and specific GIP receptor antagonists.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4 / metabolism
  • Exenatide
  • Gastric Inhibitory Polypeptide / agonists
  • Gastric Inhibitory Polypeptide / chemistry
  • Gastric Inhibitory Polypeptide / physiology
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / chemistry
  • Glucagon-Like Peptide 1 / physiology
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / therapeutic use*
  • Liraglutide
  • Molecular Sequence Data
  • Peptides
  • Receptors, Gastrointestinal Hormone / antagonists & inhibitors
  • Venoms

Substances

  • Hypoglycemic Agents
  • Incretins
  • Peptides
  • Receptors, Gastrointestinal Hormone
  • Venoms
  • Gastric Inhibitory Polypeptide
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide
  • gastric inhibitory polypeptide receptor
  • Dipeptidyl Peptidase 4