DPP-IV Inhibitors (Gliptins) for Type 2 Diabetes

From New Treatment Wiki

Jump to: navigation, search

Gliptins are novel therapeutic agents that inhibit the ubiquitous enzyme, Dipeptidyl Peptidase-IV (DPP-IV) in patients with type 2 diabetes.

DPP-4 is widely distributed, existing both as a membrane-anchored cell-surface peptidase and as a smaller soluble form in blood plasma. In humans, DPP-4 is expressed in epithelial cells, capillary endothelia and lymphocytes. This includes expression in the gastrointestinal tract, biliary tract, exocrine pancreas acinar cells, kidney, thymus, lymph nodes, uterus, placenta, prostate, the adrenal, parotid, sweat and mammary glands, liver, spleen, lungs and brain

DPP-IV rapidly metabolises the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) resulting in their reduced bioavailability and rapid inactivation in the circulation. GLP-1 and GIP are incretin hormones, released in response to nutrient stimulation and act to augment nutrient-induced insulin release in a glucose dependent manner. DPP-4 inhibitors (alogliptin, dutogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin) correct the GLP-1 deficiency by blocking this degradation, prolonging the incretin effect and enhancing glucose homoeostasis.

Clinical trials of DPP-IV inhibitors have demonstrated significant glycaemic efficacy, including sustained HbA1c (glycated haemoglobin A1c) reductions for up to 2 years in patients treated with monotherapy and combination therapy. Advantages over existing diabetes treatments include a low risk of hypoglycaemia, a neutral effect on body weight and the potential, based on animal and in vitro studies, for preservation or enhancement of β-cell function.

Contents


Latest treatments based on Gliptins

A number of DPP-4 inhibitors are in various phases of clinical development. The latest treatments and drugs based on gliptins include

  • SSR 162369 Phase 1 Sanofi-Aventis
  • TS-021 Phase 1 Taisho
  • ALS 2-0426 for Type 2 Diabetes Phase 2 Amgen/Servier
  • GRC 8200 Phase 2 Glenmark
  • PF-00734200 Phase 2 Pfizer
  • SYR-472 Phase 2 Takeda
  • TA-6666 Phase 2 Mitsubishi/Tanabe
  • Dutogliptin for Type 2 Diabetes Phase 3 Phenomix
  • Linagliptin Phase 3 Boehringer Ingelheim
  • Alogliptin Filed to FDA Takeda
  • Glavus (vildagliptin) for Type 2 Diabetes Filed to FDA; approved in EU Novartis
  • Saxagliptin Approved by FDA; filed in EU Bristol-Myers Squibb/AstraZeneca
  • Januvia (sitagliptin)

Ongoing clinical trials for Gliptins

  1. Type 2 Diabetes study in North Carolina investigating dutogliptin for patients who are currently treated with glimepiride (Amaryl).
Retrieved from "http://trialx.com/treatment/DPP-IV_Inhibitors_(Gliptins)_for_Type_2_Diabetes"
Personal tools