PMID- 23231438
OWN - NLM
STAT- MEDLINE
DCOM- 20130702
LR  - 20220419
IS  - 1746-045X (Electronic)
IS  - 1746-0441 (Linking)
VI  - 8
IP  - 2
DP  - 2013 Feb
TI  - Discovery and development of exenatide: the first antidiabetic agent to leverage 
      the multiple benefits of the incretin hormone, GLP-1.
PG  - 219-44
LID - 10.1517/17460441.2013.741580 [doi]
AB  - INTRODUCTION: The GLP-1 receptor agonist exenatide is synthetic exendin-4, a 
      peptide originally isolated from the salivary secretions of the Gila monster. 
      Exenatide was developed as a first-in-class diabetes therapy, with immediate- and 
      extended-release formulations. In preclinical diabetes models, exenatide enhanced 
      glucose-dependent insulin secretion, suppressed inappropriately elevated glucagon 
      secretion, slowed gastric emptying, reduced body weight, enhanced satiety, and 
      preserved pancreatic beta-cell function. In clinical trials, both exenatide 
      formulations reduced hyperglycemia in patients with type 2 diabetes mellitus 
      (T2DM) and were associated with weight loss. AREAS COVERED: This article reviews 
      the development of exenatide from its discovery and preclinical investigations, 
      to the elucidation of its pharmacological mechanisms of action in mammalian 
      systems. The article also presents the pharmacokinetic profiling and toxicology 
      studies of exenatide, as well as its validation in clinical trials. EXPERT 
      OPINION: GLP-1 receptor agonists represent a new paradigm for the treatment of 
      patients with T2DM. By leveraging incretin physiology, a natural regulatory 
      system that coordinates oral nutrient intake with mechanisms of metabolic 
      control, these agents address multiple core defects in the pathophysiology of 
      T2DM. Studies have identified unique benefits including improvements in glycemic 
      control and weight, and the potential for beneficial effects on the 
      cardiometabolic system without the increased risk of hypoglycemia associated with 
      insulin therapy. Peptide hormone therapeutics can offer significant advantages 
      over small molecule drug targets when it comes to specificity, potency, and more 
      predictable side effects. As exemplified by exenatide, injectable peptides can be 
      important drugs for the treatment of chronic diseases, such as T2DM.
FAU - Parkes, David G
AU  - Parkes DG
AD  - Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121, USA. 
      David.Parkes@amylin.com
FAU - Mace, Kenneth F
AU  - Mace KF
FAU - Trautmann, Michael E
AU  - Trautmann ME
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20121212
PL  - England
TA  - Expert Opin Drug Discov
JT  - Expert opinion on drug discovery
JID - 101295755
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Incretins)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
MH  - Animals
MH  - Clinical Trials as Topic
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Exenatide
MH  - Glucagon-Like Peptide 1/*metabolism
MH  - Humans
MH  - Hypoglycemic Agents/pharmacokinetics/*pharmacology
MH  - Incretins/*metabolism
MH  - Models, Animal
MH  - Peptides/pharmacokinetics/*pharmacology
MH  - Venoms/pharmacokinetics/*pharmacology
EDAT- 2012/12/13 06:00
MHDA- 2013/07/03 06:00
CRDT- 2012/12/13 06:00
PHST- 2012/12/13 06:00 [entrez]
PHST- 2012/12/13 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
AID - 10.1517/17460441.2013.741580 [doi]
PST - ppublish
SO  - Expert Opin Drug Discov. 2013 Feb;8(2):219-44. doi: 10.1517/17460441.2013.741580. 
      Epub 2012 Dec 12.