Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.
OBJECTIVE
This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone.


METHODS
Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. Changes in HbA1c and fasting plasma glucose (FPG) values were measured.


RESULTS
The combination therapy showed a significant reduction in mean HbA1c values (-1.7%) that was greater than with either type of monotherapy Repaglinide monotherapy resulted in a reduction of HbA1c values that was significantly greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43 mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in all groups.


CONCLUSIONS
Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.
Raskin
P
P
University of Texas Southwest Medical Center, Dallas 75390, USA. praski@mednet.swmed.edu
Jovanovic
L
L
Berger
S
S
Schwartz
S
S
Woo
V
V
Ratner
R
R
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D002839:Chromans / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D015415:Biomarkers; D001786:Blood Glucose; D002219:Carbamates; D002839:Chromans; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010880:Piperidines; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; C072379:repaglinide