Repaglinide versus glyburide: a one-year comparison trial

This prospective, 1-year, multicenter, double-blind, randomized, parallel-g roup study was designed to show that repaglinide was at least equivalent to glyburide in patients with type 2 diabetes. Five hundred and seventy-six p atients with type 2 diabetes of at least 6 months' duration were randomized to receive monotherapy with repaglinide (n = 383) or glyburide (n = 193). During weeks 1-8, doses were gradually increased to achieve a target fastin g plasma glucose (FPG) range of 80-140 mg/dl. The final adjusted dose was m aintained for 12 months. Repaglinide patients received a starting dose of 0 .5 mg three times/day preprandially, adjusted as necessary to 1, 2 or 4 mg before breakfast, lunch and dinner. Glyburide patients received a starting dose of 2.5 mg before breakfast and placebo before lunch and dinner. Glybur ide was increased as necessary to 5 or 10 mg before breakfast (placebo befo re lunch and dinner) or to 15 mg (10 mg before breakfast, placebo before lu nch, and 5 mg before dinner). After study drug was stopped, patients were t ransferred to an appropriate therapy, as recommended by the investigator. E fficacy was assessed by changes from baseline in glycemic control parameter s and in C-peptide, insulin, and lipid profiles. Repaglinide provided glyce mic control that was at least as effective and potentially safer than that provided by glyburide. The glucose-lowering effect of repaglinide was most pronounced in pharmacotherapy-naive patients, who showed rapid and marked d ecreases in mean glycosylated hemoglobin levels from baseline (9.4%) to mon th 3 (7.6%) and month 12 (7.9%). Mean FPG levels also decreased overall in this group, from 222 mg/dl at baseline, to 175 mg/dl at month 3, to 188 mg/ dl at month 12. At endpoint, morning C-peptide levels had increased signifi cantly in glyburide-treated patients compared with those treated with repag linide, but morning fasting insulin levels did not differ significantly bet ween the two groups. Repaglinide efficacy was sustained over 1 year and was not influenced by age or sex. Overall safety and changes in lipid profile and body weight were similar with both agents, with no significant change a fter extended pharmacotherapy. Weight gain data for the subset of pharmacot herapy-naive patients suggest that patients given repaglinide may gain less weight than those given glyburide. Repaglinide, at doses of 0.5-4.0 mg adm inistered three times preprandially, was well tolerated and provided safe a nd consistently effective glycemic control during this 1-year study. Patien ts using repaglinide received the same therapeutic benefits as those using glyburide, and may have received additional benefits. (C) 1999 Elsevier Sci ence Ireland Ltd. All rights reserved.