Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients.
OBJECTIVE
Glibenclamide attenuates the protective responses to opening of vascular ATP-sensitive potassium (K(ATP)) channels during ischaemia. Therefore, glibenclamide treatment of Type 2 diabetes mellitus may have hazardous cardiovascular effects when used under conditions of ischaemia. Glimepiride and metformin seem to lack such characteristics. Based on these data, we hypothesized that, in contrast to glibenclamide, chronic treatment of Type 2 diabetic patients with glimepiride or metformin will not impair the vasodilator function of K(ATP) opening in vivo.


METHODS
Two groups of 12 Type 2 diabetes mellitus patients participated in a double-blind randomized cross-over study consisting of two 8-week periods, in which treatment with orally administered glibenclamide (15 mg/day) was compared with either glimepiride or metformin (6 mg and 1500 mg/day, respectively). At the end of each treatment period, the increase in forearm blood flow (FBF, venous occlusion plethysmography) in response to intra-arterial administered diazoxide (K(ATP) opener), acetylcholine (endothelium-dependent vasodilator) and dipyridamole (adenosine-uptake blocker) and to forearm ischaemia was measured.


RESULTS
There were no significant differences in vasodilator responses to diazoxide, acetylcholine, dipyridamole and forearm ischaemia after glibenclamide compared with glimepiride and metformin.


CONCLUSIONS
Chronic treatment of Type 2 diabetes mellitus with glimepiride or metformin has similar effects on vascular K(ATP) channels compared with chronic glibenclamide treatment.
Abbink
E J
EJ
Division of General Internal Medicine, Department of Medicine, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Pickkers
P
P
Jansen van Rosendaal
A
A
Lutterman
J A
JA
Tack
C J
CJ
Russel
F G M
FG
Smits
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003981:Diazoxide / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D002096:C-Peptide; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D004176:Dipyridamole; C057619:glimepiride; D008687:Metformin; D000109:Acetylcholine; D003981:Diazoxide; D005905:Glyburide