Effects of a new oral hypoglycaemic agent (CS-045) on metabolic abnormalities and insulin resistance in type 2 diabetes.
The effects of a thiazolidinedione antidiabetic agent (CS-045) on diabetic metabolic abnormalities were studied in a double-blind clinical trial. Fourteen patients with Type 2 diabetes were selected according to study criteria. Eight were treated with oral CS-045 at 400 mg daily, and six were given placebo. A multi-step, hyperinsulinaemic, euglycaemic clamp study, with simultaneous plasma free fatty acid study, and glucagon tolerance test were performed before and after administration of drug. Following 3 months of treatment with CS-045, there were significant decreases in the mean levels of fasting plasma glucose (from 9.18 +/- 0.95 to 7.78 +/- 0.44 mmol l-1), postprandial plasma glucose (from 11.8 +/- 1.23 to 10.36 +/- 1.06 mmol l-1), and haemoglobin A1c (from 9.3 +/- 0.4 to 6.8 +/- 0.4%). Insulin sensitivity also improved (1st step: from 3.12 +/- 0.33 to 4.70 +/- 0.47 mg kg-1 min-1 (p < 0.01); 2nd step: from 5.61 +/- 0.63 to 7.54 +/- 0.58 mg kg-1 min-1 (p < 0.01); 3rd step: from 9.21 +/- 0.67 to 11.10 +/- 0.87 mg kg-1 min-1). The fasting free fatty acid level decreased significantly from 0.28 +/- 0.04 to 0.22 +/- 0.02 g l-1. The residual free fatty acid level (%) under insulin infusion clamp conditions decreased significantly from 63.7 +/- 9.7 to 45.0 +/- 9.2%. CS-045 treatment was associated with decrease in total cholesterol, total triglycerides, and increase in HDL cholesterol. Basal C-peptide immunoreactivity level decreased, but there was no change in the peak C-peptide immunoreactivity value.(ABSTRACT TRUNCATED AT 250 WORDS)
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
K
K
Mimura
F
F
Umeda
S
S
Hiramatsu
S
S
Taniguchi
Y
Y
Ono
N
N
Nakashima
K
K
Kobayashi
M
M
Masakado
Y
Y
Sako
H
H
Nawata
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D010919:Placebos; D012016:Reference Values; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone