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.
OBJECTIVE
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 micro mol l-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.
Dhindsa
Pash
P
School of Medical & Surgical Sciences, University of Nottingham, and Southern Derbyshire Acute Hospitals Trust, Derby, UK.
Davis
Karl R
KR
Donnelly
Richard
R
D000368:Aged; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005907:Gliclazide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D008687:Metformin; D005907:Gliclazide