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, crossover study was condu cted to characterize the new sulfonylurea glimepiride and to compare its pr ofile of action with the second generation sulfonylurea glibenclamide. The total duration of each experiment was 5 hours. At zero time an i.v. inj ection 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 af ter the injection (0-3 hours, preprandial experiment). At 3 hours, a standa rd mixed meal was given (20% of a 30 Kcal/Kg Body Weight diet) and blood sa mples were collected for 2 more hours (postprandial experiment). Pre-prandially (0-3 hrs) blood glucose (expressed as the area under the cur ve divided by the time) was significantly lower (p < 0.0001) after the admi nistration of 2 and 4 mg glimepiride (3.8 +/- 0.22 and 3.5 +/- 10.3 mM resp ectively) compared to placebo (4.63 +/- 0.31 mM), but not compared to glibe nclamide. Insulin and C-peptide were not different after glimepiride or gli benclamide. Both glimepiride and glibenclamide had similar effects on insul in secretion. Post-prandially (3-5 hrs) blood glucose was significantly hig her after glibenclamide (6.54 +/- 0.8 mM) (p < 0.0001) than after 2 mg glim epiride (5.75 +/- 0.5 mM). Despite this C-peptide was significantly higher (p < 0.002) glibendamide (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 simi lar effects on the changes in blood glucose levels after TV administration. After the meal, less pronounced hyperglycemia and lower insulin and C-pept ide levels following glimepiride (2 mg) suggests either that glimepiride in duces insulin secretion through a pathway which is different from that of g libenclamide or that glimepiride facilitates insulin action through extrapa ncreatic effects.