Efficacy and safety of combination therapy: Repaglinide plus metformin versus nateglinide plus metformin

Philip Raskin, Leslie Klaff, Janet McGill, Stephen A. South, Priscilla Hollander, Naum Khutoryansky, Paula M. Hale

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84 Scopus citations


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 HbA11c 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 HbA1c (-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 HbA1c and FPG values that were significantly greater than the reductions observed for addition of nateglinide.

Original languageEnglish
Pages (from-to)2063-2068
Number of pages6
JournalDiabetes care
Issue number7
StatePublished - Jul 1 2003


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