Effects of glimepiride vs glibenclamide on ischaemic heart disease risk factors and glycaemic control in patients with type 2 diabetes mellitus

Objective: This study aimed to compare the effects of glimepiride and glibenclamide on glycaemic control and a range of risk factors for ischaemic heart disease (IHD), including concentrations of insulin-like molecules. Patients: A double-blind, placebo-controlled, randomised, crossover comparison of 4 weeks of treatment with glibenclamide 2.5 to 20 mg/day and glimepiride 1 to 8 mg/day was undertaken in 29 type 2 (non-insulin-dependent) diabetic patients. The average (mean +/- SD) duration of diabetes was 8.5 (+/-5.9) years. Results: Compared with placebo, fasting plasma glucose was significantly lower on both drugs [placebo (P): mean (SD) 11.9 (3.3) mmol/L, glibenclamide: 9.5 (3.2); p < 0.0005, glimepiride: 10.6 (3.4); p = 0.01] and lower on glibenclamide than glimepiride (p = 0.003). The integrated, meal-stimulated rise in glucose was lower with glimepiride, but not glibenclamide, compared with placebo [P: 588.1(372.2) mmol/l.min, glimepiride: 443.0 (346.9) mmol/l.min; p = 0.010, glibenclamide: 586.4 (366.2) mmol/l.min; p = 0.630]. There was no between-drug difference (p = 0.145). Fasting insulin did not differ compared with placebo [P: 92.3 (61.3) pmol/L, glimepiride: 91.8 (60.6) pmol/L; p = 0.787, glibenclamide: 87.8 (51.6) pmol/L; p = 0.379] and there was no between-drug difference (p = 0.601). There were no significant differences in effect upon fasting concentrations of C-peptide, proinsulin, des 31,32 proinsulin or the ratio of proinsulin-like to total insulin-like molecules. The integrated insulin and C-peptide responses to a meal were significantly greater on both drugs than on placebo [insulin: median (25th, 75th percentile), P: 7073 (2430-18296) pmol/L.min, glibenclamide: 18045 (4290-35850) pmol/L.min; p = 0.0005, glimepiriae: 14355 (5880-32820) pmol/L.min; p = 0.0001; C-peptide mean (SD): P: 51.89 (49.01) nmol/L.min, glibenclamide: 90.15 (59.44) nmol/L.min; p = 0.006, glimepiride: 89.75 (61.78) nmol/L.min; p = 0.007], but there was no between-drug difference [integrated insulin (p = 0.923), integrated C-peptide (p = 0.680)]. Compared with placebo, plasminogen activator inhibitor (PAI) antigen was significantly lower on glibenclamide but not glimepiride [P: 28.8 (19.7) mu g/L, glimepiride: 24.4 (15.2) mu g/L; p = 0.300, glibenclamide: 20.0 (10.9) mu g/L; p = 0.003]. PAI activity was similar with all agents, as was low density lipoprotein (LDL)-cholesterol [P: 4.4 (1.2) mmol/L glimepiride: 4.2 (0.9) mmol/L; p = 0.225, glibenclamide: 4.5 (1.4) mmol/L; p = 0.174]. Corrected for fasting plasma glucose, LDL was 0.5 mmol/L lower on glimepiride than on glibenclamide (95% confidence interval: -0.8, -0.2), a clinically significant difference. There were no significant differences in other measured factors. Conclusion: Both drugs improved glycaemia without adversely affecting a range of IHD risk factors.