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document
Enhancement of blood glucose lowering effect of a sulfonylurea when coadministered with an ACE inhibitor : results of a glucose-clamp study . BACKGROUND To investigate if coadministration of enalapril alters the metabolic effect of glibenclamide by employing an euglycemic glucose-clamp technique in healthy volunteers . METHODS A double-blind crossover study with nine healthy normotensive volunteers ( age 27 +/- 3 y , BMI 23.3 +/- 2.0 kg m ( -2 ) ; mean +/- SD ) -randomly assigned to a 3-day treatment of either 5 mg enalapril or placebo . In the morning of the fourth day , volunteers orally received 3.5 mg glibenclamide together with either 10 mg enalapril or placebo . Blood glucose levels of volunteers were allowed to fall by 10 % from fasting levels and were kept constant thereafter by employing a Biostator-based euglycemic glucose clamp . RESULTS Coadministration of enalapril-compared with placebo-resulted in a temporarily higher metabolic effect of glibenclamide ( AUC GIR ( 0-120 ) 229 +/- 173 vs 137 +/- 44 mg kg ( -1 ) , p < 0.01 ; mean +/- SD ) , which lasted from 120 min to 240 min after enalapril administration . In parallel , the maximal metabolic effect of glibenclamide tended to be higher with enalapril ( GIR ( max ) 5.2 +/- 1.9 vs 4.1 +/- 1.3 mg kg ( -1 ) min ( -1 ) ; p = 0.19 ) . However , the total metabolic effect of glibenclamide was almost identical between volunteers taking enalapril or placebo ( AUC GIR ( 0-600 ) 1267 +/- 334 vs 1286 +/- 249 mg kg ( -1 ) , ns ) . In contrast , serum insulin levels , C-peptide levels , and serum glibenclamide profiles were not significantly different between enalapril and placebo . CONCLUSIONS The results of this study may explain the higher incidence of hypoglycemic episodes observed in patients with type 2 diabetes when taking ACE inhibitors together with sulfonylureas or insulin . ACE inhibitors may cause a temporary increase of the insulin sensitivity , which leads to an increased risk of hypoglycemia under these conditions .
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Intervention_Pharmacological
sulfonylurea
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Intervention_Pharmacological
ACE inhibitor :
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Intervention_Pharmacological
enalapril
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Intervention_Pharmacological
glibenclamide
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Intervention_Pharmacological
5 mg enalapril
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Intervention_Control
placebo
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Intervention_Pharmacological
glibenclamide
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Intervention_Pharmacological
enalapril
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Intervention_Control
placebo
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Intervention_Physical
Biostator-based euglycemic glucose clamp
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Intervention_Pharmacological
enalapril-compared
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Intervention_Control
placebo-resulted
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Intervention_Pharmacological
glibenclamide
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Intervention_Pharmacological
enalapril
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Intervention_Pharmacological
glibenclamide
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Intervention_Pharmacological
enalapril
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Intervention_Pharmacological
glibenclamide
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Intervention_Pharmacological
enalapril
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Intervention_Control
placebo
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Intervention_Pharmacological
glibenclamide
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Intervention_Pharmacological
enalapril
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Intervention_Control
placebo
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Intervention_Pharmacological
ACE inhibitors
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Intervention_Pharmacological
sulfonylureas
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Intervention_Pharmacological
insulin
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Intervention_Pharmacological
ACE inhibitors
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Outcome_Physical
Enhancement of blood glucose lowering effect
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Outcome_Physical
Blood glucose levels
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Outcome_Physical
metabolic effect of glibenclamide
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Outcome_Physical
maximal metabolic effect of glibenclamide
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Outcome_Physical
total metabolic effect of glibenclamide
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Outcome_Physical
serum insulin levels
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Outcome_Physical
C-peptide levels
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Outcome_Physical
serum glibenclamide profiles
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Outcome_Physical
hypoglycemic episodes
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Outcome_Physical
insulin sensitivity
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Outcome_Physical
increased risk of hypoglycemia
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Participant_Age
age 27 +/- 3 y