A pilot clinical trial of a new oral hypoglycemic agent, CS-045, in patients with non-insulin dependent diabetes mellitus.
CS-045, (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramkethylchroman-2- ylmethoxy)benzyl]-2,4-thiazolidinedione, lowers plasma glucose in several animal models of non-insulin dependent diabetes mellitus (NIDDM) presumably by increasing insulin sensitivity. Little adverse effect was found in a phase 1 study on healthy male subjects. In order to test its efficacy in lowering plasma glucose in NIDDM in man, a pilot multi-center clinical trial of CS-045 was carried out in 146 patients with NIDDM whose glycemic control was inadequate (FPG greater than 140 mg/dl) on diet and/or other oral hypoglycemic agents. CS-045 was given orally in a daily dose of 200 mg or 400 mg for 12 weeks in addition to the previous treatment. The mean fasting plasma glucose (FPG) and fructosamine began to decrease within 2 weeks and the mean HbA1c within 8 weeks. After 12 weeks, the FPG fell from 192 +/- 41 to 155 +/- 45 mg/dl (P less than 0.01), fructosamine from 3.7 +/- 0.6 to 3.3 +/- 0.6 (P less than 0.01), and HbA1c from 8.9 +/- 1.5 to 8.1 +/- 1.5% (P less than 0.01). The drug was effective in 39% of patients in that FPG fell by more than 20% of the initial value. This rate of efficacy was the same when CS-045 was given alone or together with other oral hypoglycemic agents. The drug was more effective in a dosage of 400 mg than with 200 mg (the rate of efficacy 46% vs 25%) and more effective in obese patients than in lean patients (46% vs 25%).(ABSTRACT TRUNCATED AT 250 WORDS)
Kuzuya
T
T
Division of Endocrinology and Metabolism, Jichi Medical School, Tochigi-ken, Japan.
Iwamoto
Y
Y
Kosaka
K
K
Takebe
K
K
Yamanouchi
T
T
Kasuga
M
M
Kajinuma
H
H
Akanuma
Y
Y
Yoshida
S
S
Shigeta
Y
Y
D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002839:Chromans / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003927:Diet, Diabetic; D005260:Female; D019270:Fructosamine; D006442:Glycated Hemoglobin / Q000032:analysis; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D015415:Biomarkers; D001786:Blood Glucose; D002839:Chromans; D019270:Fructosamine; D006442:Glycated Hemoglobin; D006595:Hexosamines; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone