Comparative effects of glimepiride and glibenclamide on blood glucose, C-peptide and insulin concentrations in the fasting and postprandial state in normal man.
A single-center, randomised, placebo- controlled, cross-over study was conducted to characterize the new sulfonylurea glimepiride and to compare its profile of action with the second generation sulfonylurea glibenclamide. The total duration of each experiment was 5 hours. At zero time an i.v. injection of 2 and 4 mg glimepiride, 1 mg glibenclamide or placebo was given i.v. to 24 healthy volunteers. Blood samples were collected for three hours after the injection (0-3 hours, preprandial experiment). At 3 hours, a standard mixed meal was given (20%, of a 30 Kcal/Kg Body Weight diet) and blood samples were collected for 2 more hours (postprandial experiment). Pre-prandially (0-3 hrs) blood glucose (expressed as the area under the curve divided by the time) was significantly lower (p < 0.0001) after the administration of 2 and 4 mg glimepiride (3.8 +/- 0.22 and 3.5 +/- 0.3 mM respectively) compared to placebo (4.63 +/- 0.31 mM), but not compared to glibenclamide. Insulin and C-peptide were not different after glimepiride or glibenclamide. Both glimepiride and glibenclamide had similar effects on insulin secretion. Post-prandially (3-5 hrs) blood glucose was significantly higher after glibenclamide (6.54 +/- 0.8 mM) (p < 0.0001) than after 2 mg glimepiride (5.75 +/- 0.5 mM). Despite this C-peptide was significantly higher (p < 0.002) glibenclamide (5.7 +/- 1.5 ng/ml) compared to glimepiride (5.1 +/- 1.3 ng/ml); the trend was the same for insulin but the results were not significantly different (p = 0.06) In conclusion, in the fasting state, glimepiride and glibenclamide had similar effects on the changes in blood glucose levels after i.v. administration. After the meal, less pronounced hyperglycemia and lower insulin and C-peptide levels following glimepiride (2 mg) suggests either that glimepiride induces insulin secretion through a pathway which is different from that of glibenclamide or that glimepiride facilitates insulin action through extrapancreatic effects.
Raptis
S A
SA
Second Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, Evangelismos Hospital, Greece.
Hatziagelaki
E
E
Dimitriadis
G
G
Draeger
K E
KE
Pfeiffer
C
C
Raptis
A E
AE
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting; D005502:Food; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005905:Glyburide