DPP-4 inhibitors

Best Pract Res Clin Endocrinol Metab. 2007 Dec;21(4):517-33. doi: 10.1016/j.beem.2007.07.005.

Abstract

Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for type-2 diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1 (GLP-1), which increases levels of active GLP-1. This increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development. Most experience so far has been with sitagliptin (Merck; approved by the FDA) and vildagliptin (Novartis; filed). These are orally active compounds with a long duration, allowing once-daily administration. Both sitagliptin and vildagliptin improve metabolic control in type-2 diabetes, both in monotherapy and in combination with metformin and thiazolidinediones. A reduction in HbA(1c) of approximately 1% is seen in studies of DPP-4 inhibition of up to 52 weeks' duration. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin. However, the durability and long-term safety of DPP-4 inhibition remain to be established.

Publication types

  • Review

MeSH terms

  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives
  • Adamantane / therapeutic use
  • Animals
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Drug Therapy, Combination
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / antagonists & inhibitors*
  • Glucagon-Like Peptide 1 / physiology
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / metabolism
  • Insulin / therapeutic use
  • Insulin Secretion
  • Lipid Metabolism / drug effects
  • Metformin / therapeutic use
  • Nitriles / adverse effects
  • Nitriles / therapeutic use
  • Pioglitazone
  • Protease Inhibitors / therapeutic use*
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use
  • Sitagliptin Phosphate
  • Substrate Specificity
  • Thiazolidinediones / therapeutic use
  • Triazoles / adverse effects
  • Triazoles / therapeutic use
  • Vildagliptin

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Nitriles
  • Protease Inhibitors
  • Pyrazines
  • Pyrrolidines
  • Thiazolidinediones
  • Triazoles
  • Glucagon-Like Peptide 1
  • Glucagon
  • Metformin
  • Vildagliptin
  • Adamantane
  • Sitagliptin Phosphate
  • Pioglitazone