Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone.
The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone.
Jovanovic
Lois
L
Sansum Medical Research Institute, 2219 Bath Street, Santa Barbara, CA 93105, USA. ljovanovic@sanmsum.org
Hassman
David R
DR
Gooch
Brent
B
Jain
Rajeev
R
Greco
Susan
S
Khutoryansky
Naum
N
Hale
Paula M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D000077205:Pioglitazone; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
D001786:Blood Glucose; D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D000077205:Pioglitazone; D010880:Piperidines; D045162:Thiazolidinediones; C072379:repaglinide