Characteristics of pancreatic beta-cell secretion in Type 2 diabetic patients treated with gliclazide and glibenclamide

Abstract

The aim of the present cross-over study was to compare the beta-cell response to gliclazide and glibenclamide administered orally during and following a hyperglycaemic clamp in sulphonylurea treated Type 2 diabetes. Nine patients (6 males), aged 61.4 (S.D. 6.9) years with a body mass index of 27.5 (3.1) kg m(-2) and HbA(1c) at baseline of 7.2 (0.9)% were included. Eight healthy control subjects underwent the same tests. Patients received 80-240 mg gliclazide or 5-15 mg glibenclamide for 6 weeks. Thirty minutes after administration of 160 mg of gliclazide or 10 mg of glibenclamide a 1-h hyperglycaemic clamp (11.0 mmol l(-1)) was begun, and followed by a 3.5-h observation period. Nadir blood glucose levels were 4.2 (1.0), 4.3 (1.2) and 3.4 (1.0) mmol l(-1) for glibenclamide gliclazide and controls, respectively (both P=0.07 vs. controls). Glucose levels decreased slowly and linearly in people with diabetes and reached nadirs after 204 (8) and 198 (18) min, respectively, after cessation of glucose infusion, while in controls, glucose levels declined steeply to a nadir at 98 (47) min (P<0.003 vs. both drugs). No first phase insulin secretion peak was observed in people with diabetes. Insulin levels remained elevated during the 3-h observation period in SU treated patients but, in control subjects decreased to baseline values within 2 h of the clamp. The proinsulin to C-peptide ratio increased during the observation period. In conclusion, the effects of glibenclamide and gliclazide on insulin secretion are very similar in patients with Type 2 diabetes who are in moderate glycaemic control, with a slow rise to lower amplitude, poor responsiveness to falling glucose levels, and raised proinsulin to C-peptide ratio.