OBJECTIVE: To study the metabolic effects of a new oral antidiabetic agent, CS-045, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Eleven NIDDM subjects (mean age 59 yr and body mass index 32.3) were treated with 400 mg/day CS-045 for 6-12 wk. Patients were hospitalized before and at the end of the drug-treatment period for metabolic studies, including oral glucose tolerance test (OGTT), meal tolerance test (MTT), euglycemic glucose-clamp studies, and lipid analyses. RESULTS: Eight subjects showed a marked clinical response to the drug, whereas 3 were nonresponders. The data were analyzed both for the total group and for the responders. Fasting plasma glucose (FPG) fell from 12.5 +/- 0.7 to 10.7 +/- 1.0 mM in the total group but fell more dramatically from 12.7 +/- 0.5 to 8.3 +/- 0.6 mM in the responder group. The area under the OGTT glucose curve improved by 17% in the total group and by 29% in the responders. The area under the MTT glucose curve improved by 38 and 52%, respectively. MTT levels of insulin, free fatty acids, and glucagon were significantly lower after treatment. Glucose disposal rates during glucose-clamp studies were increased in all subjects after CS-045 treatment. Mean increases were 63% at 120 mU.m-2.min-1 and 41% at 300 mU.m-2.min-1. Basal hepatic glucose production fell by 17% in the total group and by 28% in the responders. CONCLUSIONS: CS-045 improves insulin resistance, reduces insulinemia, lowers hepatic glucose production, and improves both fasting and postprandial glycemia in NIDDM subjects. CS-045 may represent a new therapeutic option for NIDDM.
OBJECTIVE: To study the metabolic effects of a new oral antidiabetic agent, CS-045, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Eleven NIDDM subjects (mean age 59 yr and body mass index 32.3) were treated with 400 mg/day CS-045 for 6-12 wk. Patients were hospitalized before and at the end of the drug-treatment period for metabolic studies, including oral glucose tolerance test (OGTT), meal tolerance test (MTT), euglycemic glucose-clamp studies, and lipid analyses. RESULTS: Eight subjects showed a marked clinical response to the drug, whereas 3 were nonresponders. The data were analyzed both for the total group and for the responders. Fasting plasma glucose (FPG) fell from 12.5 +/- 0.7 to 10.7 +/- 1.0 mM in the total group but fell more dramatically from 12.7 +/- 0.5 to 8.3 +/- 0.6 mM in the responder group. The area under the OGTT glucose curve improved by 17% in the total group and by 29% in the responders. The area under the MTT glucose curve improved by 38 and 52%, respectively. MTT levels of insulin, free fatty acids, and glucagon were significantly lower after treatment. Glucose disposal rates during glucose-clamp studies were increased in all subjects after CS-045 treatment. Mean increases were 63% at 120 mU.m-2.min-1 and 41% at 300 mU.m-2.min-1. Basal hepatic glucose production fell by 17% in the total group and by 28% in the responders. CONCLUSIONS:CS-045 improves insulin resistance, reduces insulinemia, lowers hepatic glucose production, and improves both fasting and postprandial glycemia in NIDDM subjects. CS-045 may represent a new therapeutic option for NIDDM.
Authors: B Zhang; M Shiomi; H Tanaka; J Mei; P Fan; Y Tsujita; H Horikoshi; K Saku Journal: Eur J Drug Metab Pharmacokinet Date: 2001 Jul-Sep Impact factor: 2.441
Authors: G D Tan; B A Fielding; J M Currie; S M Humphreys; M Désage; K N Frayn; M Laville; H Vidal; F Karpe Journal: Diabetologia Date: 2004-12-24 Impact factor: 10.122
Authors: M Kellerer; M Coghlan; E Capp; A Mühlhöfer; G Kroder; L Mosthaf; P Galante; K Siddle; H U Häring Journal: J Clin Invest Date: 1995-07 Impact factor: 14.808
Authors: T A Buchanan; W P Meehan; Y Y Jeng; D Yang; T M Chan; J L Nadler; S Scott; R K Rude; W A Hsueh Journal: J Clin Invest Date: 1995-07 Impact factor: 14.808