Metabolic effects of new oral hypoglycemic agent CS-045 in NIDDM subjects

• Published in: Diabetes care Vol. 15; no. 2; pp. 193 - 203
• Main Authors: SUTER, S. L, NOLAN, J. J, WALLACE, P, GUMBINER, B, OLEFSKY, J. M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.1992
• Subjects: Biological and medical sciences; Blood Glucose - metabolism; Cholesterol - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Chromans - therapeutic use; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Fatty Acids, Nonesterified - blood; Female; Glucagon - blood; Gluconeogenesis; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hypoglycemic Agents - therapeutic use; Insulin - blood; Liver - metabolism; Male; Medical sciences; Middle Aged; Muscle; Pharmacology. Drug treatments; Thiazoles - therapeutic use; Thiazolidinediones; Triglycerides - blood; Troglitazone; Endocrinopathy; Human; Chemotherapy; Hypoglycemic agent; Treatment; Oral administration; Metabolism; Non insulin dependent diabetes
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.15.2.193

Metabolic effects of new oral hypoglycemic agent CS-045 in NIDDM subjects. S L Suter , J J Nolan , P Wallace , B Gumbiner and J M Olefsky Department of Medicine, University of California, San Diego, La Jolla 92093. Abstract 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.