Background: The more rapid onset of action and the shorter half-life of repaglinide may reduce the post-load glucose excursion and limit sustained insulin secretion compared to sulphonylurea (SU) derivatives.
Methods: We studied 12 patients with type 2 diabetes (age 62 +/- 2 years, BMI 28.3 +/- 1.3 kg m(-2), HbA1c 6.7 +/- 0.2%) on SU monotherapy at submaximal dose. Patients were treated for 3 weeks with repaglinide or glibenclamide in a randomized, crossover trial. At the end of each treatment period, patients underwent a 60-min hyperglycaemic clamp (glucose 12 mmol L(-1)) followed by 4-h observation (60-300 min) with frequent blood sampling for determination of glucose, insulin, proinsulin and C-peptide levels. Before the clamp (5 min for repaglinide, 30 min for glibenclamide), patients ingested their usual morning drug dose.
Results: After the end of the hyperglycaemic clamp, mean plasma glucose fell to a level of 5 mmol L(-1) after approximately 150 min with repaglinide, and after approximately 190 min with glibenclamide. While initially quite similar, in the period from 240 to 300 min, insulin, proinsulin and C-peptide levels were lower during repaglinide treatment (insulin 133 +/- 20 vs 153 +/- 25 pmol L(-1) (P < 0.05), proinsulin 14 +/- 3 vs 19 +/- 4 pmol L(-1) (P = 0.06) and C-peptide 0.81 +/- 0.19 vs 1.14 +/- 0.18 nmol L(-1) (P = 0.05) for repaglinide vs glibenclamide, respectively).
Conclusions: Following glucose stimulation, plasma glucose levels, and insulin concentration decrease more rapidly after repaglinide treatment than after glibenclamide. Proinsulin and C-peptide secretion tended to fall more rapidly as well. These findings are consistent with a more rapid onset and shorter duration of beta-cell stimulation associated with repaglinide.
Copyright 2004 John Wiley & Sons, Ltd.