Proportional Dose-Response Relationship and Lower Within-Patient Variability of Insulin Detemir and NPH Insulin in Subjects With Type 1 Diabetes Mellitus

Abstract

Aims: This study was conducted to evaluate the dose ratio of insulin detemir and neutral protamine Hagedorn (NPH) insulin over a range of therapeutically relevant subcutaneous doses.

Methods: The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of insulin detemir (0.15, 0.3, 0.6 U/kg) and NPH insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6-²H₂] glucose).

Results: Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U insulin detemir equals 1 IU NPH insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUC_GIR) and the maximal GIR (GIR_max) values, when comparing U (insulin detemir) to IU (NPH insulin). The pharmacodynamic within-subject profile was lower with insulin detemir in regard to AUC_{GIR 0-24 h}, GIR_max and duration of action (P<0.05). There was a tendency for a greater reduction of EGP with insulin detemir than with NPH insulin in regard to the area over the curve (AOC) of EGP in 24 hours (AOC_{EGP 0-24 h}) (P=0.07) and minimal EPG (EGP_min) (P=0.02).

Conclusions: These data show that insulin detemir is dose-proportional to NPH insulin in type 1 diabetic patients at clinically relevant doses. The data indicate that insulin detemir has a lower degree of within-subject variability.

Glucose uptake - glucose production - glucose clamp - tracer infusion technique

References

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