SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans.
Adult
Aged
Blood Glucose
/ drug effects
Diabetes Mellitus, Type 2
/ blood
Double-Blind Method
Gastrointestinal Hormones
/ metabolism
Glucose Intolerance
/ drug therapy
Glucose Tolerance Test
Glycemic Control
/ methods
Humans
Insulin Secretion
/ drug effects
Islets of Langerhans
/ drug effects
Japan
Male
Middle Aged
Piperidines
/ administration & dosage
Pyridines
/ administration & dosage
Receptors, G-Protein-Coupled
/ agonists
Young Adult
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
21
05
2021
accepted:
20
07
2021
pubmed:
30
7
2021
medline:
22
12
2021
entrez:
29
7
2021
Statut:
ppublish
Résumé
SCO-267 is a full agonist of the free fatty acid receptor 1 (GPR40), which regulates the secretion of islet and gut hormones. In this phase 1 study, we aimed to evaluate the clinical profile of single and multiple once-daily oral administration of SCO-267 in healthy adults and patients with diabetes. Plasma SCO-267 concentration was seen to increase in a dose-dependent manner after administration, and its plasma exposure was maintained for 24 h. Repeated dose did not alter the pharmacokinetic profile of SCO-267 in healthy adults. SCO-267 was generally safe and well tolerated at all evaluated single and multiple doses. Single and repeated doses of SCO-267 stimulated the secretion of insulin, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and peptide YY in healthy adults. Furthermore, a single dose of SCO-267 stimulated the secretion of these hormones, decreased fasting hyperglycemia, and improved glycemic control during an oral glucose tolerance test in patients with diabetes, without inducing hypoglycemia. This study is the first to demonstrate the clinical effects of a GPR40 full agonist. SCO-267 is safe and well tolerated and exhibits once-daily oral dosing potential. Its robust therapeutic effects on hormonal secretion and glycemic control make SCO-267 an attractive drug candidate for the treatment of diabetes.
Identifiants
pubmed: 34321316
pii: db21-0451
doi: 10.2337/db21-0451
pmc: PMC8571351
doi:
Substances chimiques
Blood Glucose
0
FFAR1 protein, human
0
Gastrointestinal Hormones
0
Piperidines
0
Pyridines
0
Receptors, G-Protein-Coupled
0
SCO-267
0
Banques de données
figshare
['10.2337/figshare.15036009']
JapicCTI
['JapicCTI-195057']
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2364-2376Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 by the American Diabetes Association.
Références
Pharmacol Toxicol. 2003 Dec;93(6):249-58
pubmed: 14675457
Endocr Rev. 2018 Oct 1;39(5):719-738
pubmed: 29905825
Handb Exp Pharmacol. 2017;236:159-180
pubmed: 27807697
JCI Insight. 2019 Mar 7;4(5):
pubmed: 30720465
Physiol Rev. 2017 Apr;97(2):721-766
pubmed: 28275047
Diabetes Obes Metab. 2016 Sep;18(9):925-9
pubmed: 27178047
J Biol Chem. 2003 Mar 28;278(13):11303-11
pubmed: 12496284
Mol Metab. 2021 Apr;46:101090
pubmed: 32987188
Mol Pharmacol. 2021 Apr;99(4):286-293
pubmed: 33547250
Cell Rep. 2018 Oct 30;25(5):1127-1134.e2
pubmed: 30380405
Diabetologia. 2014 Sep;57(9):1762-9
pubmed: 24917132
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7123-7128
pubmed: 30872479
Nature. 2003 Mar 13;422(6928):173-6
pubmed: 12629551
JCI Insight. 2019 Jul 23;5:
pubmed: 31335319
Lancet. 2012 Apr 14;379(9824):1403-11
pubmed: 22374408
PLoS One. 2012;7(10):e46300
pubmed: 23056280
J Pharmacol Exp Ther. 2019 Aug;370(2):172-181
pubmed: 31182471
J Med Chem. 2020 Sep 24;63(18):10352-10379
pubmed: 32900194
Endocrinology. 2020 Nov 1;161(11):
pubmed: 32964214
ACS Med Chem Lett. 2012 Aug 15;3(9):726-30
pubmed: 24900539
Diabetes. 2014 Nov;63(11):3711-20
pubmed: 24939425
JCI Insight. 2019 Apr 23;5:
pubmed: 31012868
Diabetes Care. 2013 Feb;36(2):245-50
pubmed: 23086138
Clin Pharmacol. 2019 May 09;11:57-65
pubmed: 31191043
J Pharmacol Exp Ther. 2020 Oct;375(1):21-27
pubmed: 32719069
Sci Adv. 2021 Mar 12;7(11):
pubmed: 33712466
Diabetes Obes Metab. 2012 Mar;14(3):271-8
pubmed: 22051148
Diabetes Obes Metab. 2018 Feb;20 Suppl 1:5-21
pubmed: 29364588