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
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 +/-
10.3 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) 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
similar effects on the changes in blood glucose levels after TV
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
