Comparison of the micro- and macro-vascular effects of glimepiride and gliclazide in metformin-treated patients with Type 2 diabetes: A double-blind, crossover study

Abstract

Aims: To compare the metabolic and vascular effects of two sulphonylureas (SU), gliclazide (specific for the pancreatic [SUR1] receptor) and glimepiride (a nonspecific agent that also binds to vascular and cardiac [SUR2] receptors), during chronic administration in metformin-treated patients with Type 2 diabetes (T2DM). Methods: A randomized, double-blind, crossover study of gliclazide 80 mg BID and glimepiride 2 mg OD, each for 4 weeks as add-on therapy to metformin, with a 4-week washout period. Patients attended four study mornings after first dose and 4 weeks' SU treatment for measurements of arterial distensibility (Ax), pressor responsiveness to i.v. angiotensin II (ANGII), and cutaneous microvascular vasodilator responses to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP).Results: Glycaemic responses were similar (e.g. serum fructosamine was 315 vs 329 μmol 1-1 after 4 weeks), and there was no change in augmentation index during treatment with either SU (9.1 vs 9.8 mmHg after 4 weeks [95% confidence interval -8.1, 10.5]). Similarly, there were no differences between treatments in pressor responsiveness (e.g. PD10, [dose of agonist required to increase mean BP by 10 mmHg] for ANGII was 1.37 vs 1.68 ng kg-1 min-1 [-4.3, 6.9]) or cutaneous microvascular vasodilator responses (peak ACh response 68 ± 36 vs 63 ± 34 perfusion units [-82.7, 79.1]). Conclusions: There is no evidence that SUR1-specific and nonspecific SUs have differential effects on arterial distensibility, endothelial function or vasodilator mechanisms in metformin-treated patients with T2DM.