Efficacy and Safety of Combination Therapy

Abstract

OBJECTIVE—An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes.

RESEARCH DESIGN AND METHODS—Enrolled patients (n = 192) had HbA_1c >7% and ≤12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide ≤2.5 mg, metformin ≤500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16.

RESULTS—Final HbA_1c values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA_1c (−1.28 vs. −0.67%; P < 0.001) and of fasting plasma glucose (FPG) (−39 vs. −21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 a.m. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens.

CONCLUSIONS—The addition of repaglinide to metformin therapy resulted in reductions of HbA_1c and FPG values that were significantly greater than the reductions observed for addition of nateglinide.