Effect of the oral hypoglycaemic sulphonylurea glibenclamide, a blocker of ATP-sensitive potassium channels, on walking distance in patients with intermittent claudication.
OBJECTIVE
The oral hypoglycaemic sulphonylurea glibenclamide stimulates endogenous insulin secretion through blockade of ATP-sensitive potassium (KATP) channels on pancreatic beta cells, but also blocks cardiovascular KATP channels, leading to increased peripheral vascular resistance and reduced peripheral blood flow in non-diabetic subjects. Therefore, this study examined whether a single oral dose of glibenclamide adversely affected the pain-free or maximal walking distance in patients with intermittent claudication.


METHODS
In a double-blind, randomized crossover study, 12 non-diabetic patients with intermittent claudication were given a single oral dose of glibenclamide (5.25 mg) or placebo separated by a washout period of 1 week. A treadmill test was carried out 180 min after glibenclamide/placebo intake for determination of pain-free and maximal walking distance. Plasma glucose concentrations were kept constant by an euglycemic clamp. Changes in ankle/brachial blood pressure index (ABI), serum insulin, and serum glibenclamide were also assessed.


RESULTS
The pain-free walking distance was 62.8 +/- 9.8 metres (mean +/- sem) after glibenclamide and 52.6 +/- 5.9 metres after placebo (P = 0.52). The maximal walking distance was 142.7 +/- 18.7 metres after glibenclamide and 132.6 +/- 16.6 metres after placebo (P = 0.23). The ABI was not significantly changed by glibenclamide compared with placebo. Serum glibenclamide was 0.51 +/- 0.08 microm 180 min after administration of the drug. Glibenclamide produced an 8-fold increase in circulating insulin compared with placebo (P < 0.001).


CONCLUSIONS
Glibenclamide given as a single oral dose commonly used in glucose-lowering drug therapy does not reduce pain-free or maximal walking distance in non-diabetic patients with intermittent claudication.
Department of Cardiology B, Aarhus University Hospital, Aarhus, Denmark.
U M
UM
Mortensen
J E
JE
Nielsen-Kudsk
H M
HM
Sondergaard
P
P
Jakobsen
B S
BS
Jensen
O
O
Schmitz
T T
TT
Nielsen
D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D005905:Glyburide / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007328:Insulin / Q000097:blood; D007383:Intermittent Claudication / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology; D011188:Potassium / Q000097:blood; D026902:Potassium Channel Blockers / Q000008:administration & dosage* / Q000097:blood; D012709:Serum Albumin / Q000032:analysis; D016138:Walking
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D026902:Potassium Channel Blockers; D012709:Serum Albumin; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide