Comparative effects of glimepiride and glibenclamide on blood glucose, C-peptide and insulin concentrations in the fasting and postprandial state in normal man

Summary

A single-center, randomised, placebo- controlled, crossover 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 IV 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-pran-dially (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 IV 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.

Key words

Sulfonylureas - glimepiride - glibenclamide - insulin secretion - blood glucose