Back to Search
Start Over
A multiple-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of a novel GPR40 agonist, TAK-875, in subjects with type 2 diabetes.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2012 Jul; Vol. 92 (1), pp. 29-39. Date of Electronic Publication: 2012 Jun 06. - Publication Year :
- 2012
-
Abstract
- G-protein-coupled receptor 40 (GPR40), highly expressed in pancreatic β-cells, mediates free fatty acid (FFA)-induced insulin secretion. This phase I, double-blind, randomized study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel, glucose-lowering GPR40 agonist, TAK-875 (q.d., orally × 14 days), in type 2 diabetics (placebo, n = 14; at 25, 50, 100, 200, or 400 mg, n = 45). Approximately dose-proportional increases in AUC(0-24) and C(max) occurred. TAK-875 showed good tolerability with no dose-limiting side effects. Two subjects (on TAK-875) had mild hypoglycemia, probably related to prolonged fasting after oral glucose tolerance tests (OGTTs). TAK-875 showed reductions from baseline in fasting (2 to -93 mg/dl) and post-OGTT glucose (26 to -172 mg/dl), with an apparent dose-dependent increase in post-OGTT C-peptide over 14 days. Consistent with preclinical data, TAK-875 apparently acts as a glucose-dependent insulinotropic agent with low hypoglycemic risk. Its PK is suitable for once-daily oral administration.
- Subjects :
- Administration, Oral
Biological Availability
Blood Glucose metabolism
C-Peptide metabolism
Diabetes Mellitus, Type 2 metabolism
Dose-Response Relationship, Drug
Double-Blind Method
Fatty Acids, Nonesterified metabolism
Glucose Tolerance Test adverse effects
Glucose Tolerance Test methods
Humans
Hypoglycemic Agents administration & dosage
Hypoglycemic Agents pharmacokinetics
Insulin metabolism
Insulin pharmacokinetics
Insulin Secretion
Insulin-Secreting Cells metabolism
Treatment Outcome
Benzofurans administration & dosage
Benzofurans pharmacology
Diabetes Mellitus, Type 2 drug therapy
Receptors, G-Protein-Coupled metabolism
Sulfones administration & dosage
Sulfones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-6535
- Volume :
- 92
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 22669289
- Full Text :
- https://doi.org/10.1038/clpt.2012.43