Summary
Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10% below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40% higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3–3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25–40% and by 30% compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per μmol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions.
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Abbreviations
- AG:
-
AG-EE 623 ZW (((S)-(+)-2-ethoxy-4-[2-((3-methyl-1-[2-(1-piperidinyl)phenyl]-butyl)amino)-2-oxoethyl)benzoic acid)
- GIR:
-
glucose infusion rate
- ANOVA:
-
analysis of variance
- AUC:
-
area under the curve
- GIRmax :
-
maximal glucose infusion rate
- Tmax :
-
time to reach GIRmax
- early T50 :
-
time to reach half-maximal glucose infusion rate before GIRmax
- late T50 :
-
time to reach half-maximal glucose infusion rate after GIRmax
- insulin-AUC:
-
AUC under the serum insulin concentration curve
- GIR-AUC:
-
AUC under the GIR curve
- Hindex :
-
hypoglycaemic index
- OHA:
-
oral hypoglycaemic agents
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Ampudia-Blasco, F.J., Heinemann, L., Bender, R. et al. Comparative dose-related time-action profiles of glibenclamide and a new non-sulphonylurea drug, AG-EE 623 ZW, during euglycaemic clamp in healthy subjects. Diabetologia 37, 703–707 (1994). https://doi.org/10.1007/BF00417695
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DOI: https://doi.org/10.1007/BF00417695