Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with type II diabetes.
OBJECTIVE
The short-term efficacy, safety and tolerability of rosiglitazone were compared with placebo in patients with Type II (non-insulin-dependent) diabetes mellitus in a dose-ranging study.


METHODS
After a 2-week placebo run-in phase, 303 patients were randomly assigned to 8 weeks of treatment with twice-daily placebo or 2, 4 or 6 mg of rosiglitazone.


RESULTS
All rosiglitazone doses significantly reduced fasting plasma glucose compared with baseline. All rosiglitazone treatment groups showed significantly reduced peak postprandial glucose concentrations compared with baseline (p < 0.001) and with placebo (p < 0.0001) and reduced postprandial glucose excursion, without an increase in the area under the postprandial insulin concentration-time curve. Rosiglitazone at 4 and 6 mg twice daily prevented the increase in HbA1c observed in the placebo group. C peptide and serum insulin concentrations were significantly reduced from baseline in all rosiglitazone treatment groups. In all rosiglitazone treatment groups, nonesterified fatty acids decreased significantly (p < 0.0001) and triglycerides did not change. Although total LDL and HDL cholesterol increased significantly in the rosiglitazone treatment groups, total cholesterol/HDL ratios did not change significantly. The proportion of patients with one or more adverse event was similar in all four treatment groups. No patient showed evidence of hepatotoxicity.


CONCLUSIONS
Rosiglitazone given twice daily significantly reduced fasting and postprandial glucose concentrations, C peptide, insulin and nonesterified fatty acids in Type II diabetic patients. The glucose-lowering effect of the 4-mg twice-daily dose of rosiglitazone was similar to that of 6-mg twice daily, suggesting that 4 mg twice daily should be the maximum clinical dose.
Raskin
P
P
University of Texas Southwestern Medical Center, Dallas, USA.
Rappaport
E B
EB
Cole
S T
ST
Yan
Y
Y
Patwardhan
R
R
Freed
M I
MI
D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000097:blood*; D005260:Female; D019270:Fructosamine / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D045162:Thiazolidinediones; D013997:Time Factors
D001786:Blood Glucose; D019270:Fructosamine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones