Medicinal chemistry and applications of incretins and DPP-4 inhibitors in the treatment of type 2 diabetes mellitus

Mohamed Lotfy, Jaipaul Singh, H. Kalász, K. Tekes, Ernest Adeghate

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.

Original languageEnglish
Pages (from-to)82-92
Number of pages11
JournalOpen Medicinal Chemistry Journal
Volume5
Issue numberSPEC. ISSUE 2
DOIs
Publication statusPublished - 2011

Fingerprint

Dipeptidyl-Peptidase IV Inhibitors
Incretins
Glucagon-Like Peptide 1
Pharmaceutical Chemistry
Type 2 Diabetes Mellitus
Insulin Receptor
Glucose
Dipeptidyl Peptidase 4
Therapeutics
Peptides
Insulin-Secreting Cells
Cough
Diabetes Mellitus
Hormones
Enzymes
Pharmaceutical Preparations

Keywords

  • DPP-4 inhibitors
  • Incretins
  • Medicinal chemistry
  • Type 2 diabetes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Medicinal chemistry and applications of incretins and DPP-4 inhibitors in the treatment of type 2 diabetes mellitus. / Lotfy, Mohamed; Singh, Jaipaul; Kalász, H.; Tekes, K.; Adeghate, Ernest.

In: Open Medicinal Chemistry Journal, Vol. 5, No. SPEC. ISSUE 2, 2011, p. 82-92.

Research output: Contribution to journalArticle

@article{97b04c512c974af5993509f15fff5529,
title = "Medicinal chemistry and applications of incretins and DPP-4 inhibitors in the treatment of type 2 diabetes mellitus",
abstract = "Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90{\%} of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.",
keywords = "DPP-4 inhibitors, Incretins, Medicinal chemistry, Type 2 diabetes",
author = "Mohamed Lotfy and Jaipaul Singh and H. Kal{\'a}sz and K. Tekes and Ernest Adeghate",
year = "2011",
doi = "10.2174/1874104501105010082",
language = "English",
volume = "5",
pages = "82--92",
journal = "Open Medicinal Chemistry Journal",
issn = "1874-1045",
publisher = "Bentham Science Publishers B.V.",
number = "SPEC. ISSUE 2",

}

TY - JOUR

T1 - Medicinal chemistry and applications of incretins and DPP-4 inhibitors in the treatment of type 2 diabetes mellitus

AU - Lotfy, Mohamed

AU - Singh, Jaipaul

AU - Kalász, H.

AU - Tekes, K.

AU - Adeghate, Ernest

PY - 2011

Y1 - 2011

N2 - Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.

AB - Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.

KW - DPP-4 inhibitors

KW - Incretins

KW - Medicinal chemistry

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=80455131061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80455131061&partnerID=8YFLogxK

U2 - 10.2174/1874104501105010082

DO - 10.2174/1874104501105010082

M3 - Article

C2 - 21966329

AN - SCOPUS:80455131061

VL - 5

SP - 82

EP - 92

JO - Open Medicinal Chemistry Journal

JF - Open Medicinal Chemistry Journal

SN - 1874-1045

IS - SPEC. ISSUE 2

ER -