Dipeptidyl peptidase-4 inhibitors

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Inhibitors of Dipeptidyl peptidase 4 , also DPP-4 inhibitors, are a new class of oral hypoglycemics which block DPP-4.

Their mechanism of action is thought to result from increased Incretin levels (GLP-1 and GIP),^[1][2][3] which, inhibit glucagon release (which increases the blood glucose) but more importantly increase insulin secretion and decrease gastric emptying.

Drugs belonging to this class are vildagliptin^[4], sitagliptin^[5], saxagliptin and alogliptin.

Although extensive long-term, pre-clinical studies of the major DPP-4 inhibitors has failed to show any evidence of potential to cause tumors in laboratory animals, there was one in-vitro (i.e., test tube) study that has raised some questions. ^[6]

Sitagliptin entered the Australian drug market in late 2007 for the treatment of difficult to control diabetes mellitus type 2.

[edit] References

1. ^ McIntosh CH, Demuth HU, Pospisilik JA, Pederson R. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents? Regul Pept. 2005 Jun 15;128(2):159-65. PMID:15780435 [1].
2. ^ Behme MT, Dupre J, McDonald TJ. Glucagon-like peptide 1 improved glycemic control in type 1 diabetes. BMC Endocr Disord. 2003 Apr 10;3(1):3. PMID 12697069. Full Free Text.
3. ^ Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, McDonald TJ. Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM. Diabetes. 1995 Jun;44(6):626-30. PMID 7789625.
4. ^ Banting and Best Diabetes Centre at UT laf237 - Vildagliptin
5. ^ Banting and Best Diabetes Centre at UT mk-0431 - Sitagliptin
6. ^ Masur K et al. DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells, Regul Pept. ,137 (3) p. 147-55 (2006) PMID 16908079.

[edit] External links

• The race to get DPP-4 inhibitors to market - Forbes.com

v • d • e Oral antidiabetic drugs and Insulin analogs (A10) Biguanides Metformin Sulfonylureas Carbutamide, Chlorpropamide, Glibenclamide (Glyburide), Gliclazide, Glimepiride, Glipizide, Gliquidone, Tolazamide, Tolbutamide Alpha-glucosidase inhibitors Acarbose, Miglitol, Voglibose Thiazolidinediones (TZD) Pioglitazone, Rivoglitazone†, Rosiglitazone, Troglitazone‡ Meglitinides Nateglinide, Repaglinide, Mitiglinide Dipeptidyl peptidase-4 (DPP-4) inhibitors Alogliptin†, Saxagliptin†, Sitagliptin, Vildagliptin Glucagon-like peptide-1 analog Exenatide, Liraglutide†, Albiglutide† Amylin analog Pramlintide Insulin analogs fast acting (Insulin lispro, Insulin aspart, Insulin glulisine), long acting (Insulin glargine, Insulin detemir), Inhalable insulin (Exubera) Dual PPAR agonists Aleglitazar†, Muraglitazar§, Tesaglitazar§ SGLT2 inhibitor Dapagliflozin†, Remogliflozin†, Sergliflozin† †Undergoing clinical trials. ‡ Withdrawn from market. §Development halted.