Similarity of pharmacodynamic effects of a single injection of insulin glargine, insulin detemir and NPH insulin on glucose metabolism assessed by 24-h euglycaemic clamp studies in healthy humans

作者: L. P. Sørensen , B. Brock , A. Mengel , J. Rungby , N. Moller

DOI: 10.1111/J.1464-5491.2010.03026.X

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摘要: Diabet. Med. 27, 830–837 (2010) Abstract Aims  Two long-acting insulin analogues, glargine and detemir, have been developed as alternatives to neutral protamine Hagedorn (NPH) insulin, which has the preferred basal preparation for decades. The aim was directly compare pharmacodynamic properties of analogues NPH after a single subcutaneous injection. Methods  study conducted double-blind, controlled, three-arm, crossover including 10 healthy lean male volunteers. On three different occasions, each subject challenged with 0.4 U kg−1 either glargine, detemir or insulin. Plasma glucose maintained at 0.3 mmol l−1 below fasting level by clamping 24 h. C-peptide, free fatty acids (FFAs) counter regulatory hormones were measured throughout clamp period, whereas endogenous release (EGR) assessed isotope dilution technique (3-3H-glucose). Results  mean infusion rate (GIR)–time profiles revealed no significant differences between preparations in primary endpoints: Maximal GIR approximately 3.4 mg kg−1 min−1 (P = 0.68), time maximal 10 h (TRmax) (P = 0.35) area under curve (GIRAUC) (P = 0.81). Compared other preparations, EGR (see above)was lower beginning period (330–360 min) (P = 0.007) while (P = 0.005) FFA concentrations higher during last 4 h clamp. Conclusions  In this experimental design, only minor demonstrated

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