Albumin‐bound basal insulin analogues (insulin detemir and NN344): comparable time‐action profiles but less variability than insulin glargine in type 2 diabetes

Diabetes, Obesity and Metabolism - Tập 9 Số 3 - Trang 290-299 - 2007
Oliver Klein1, Jan Lynge2, Lars Endahl2, Birgitte Bentz Damholt2, Leszek Nosek1, Tim Heise1
1Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany
2Novo-Nordisk, Bagsvaerd, Denmark

Tóm tắt

Aim:  This study compared the time‐action profiles of the novel albumin‐bound basal insulin analogue NN344 with those of insulin detemir and insulin glargine in individuals with type 2 diabetes.Methods:  Twenty‐seven insulin‐treated men with type 2 diabetes [body mass index 30.8 ± 2.6 kg/m2 (mean ± s.d.), haemoglobin A1c 7.6 ± 1.1%] were enrolled in this randomized, double‐blind trial and participated in six euglycaemic glucose clamp experiments [target blood glucose (BG) 5 mmol/l] each. Participants received NN344 in three experiments at a dose of 0.8, 1.6 and 2.8 dosing units (DU) (1 DU corresponds to 6 nmol NN344) per kilogram of body weight. In the other three experiments, the participants received 0.4, 0.8 and 1.4 U/kg of either insulin detemir or insulin glargine. The insulin preparations were characterized with regards to their effects on glucose infusion rates (GIRs) (in particular duration of action and within‐subject and between‐subject variabilities), BG, C‐peptide, free fatty acids (FFA), endogenous glucose production (EGP) and peripheral glucose uptake (PGU) over 24 h post‐dose.Results:  The mean GIR profiles for all three preparations were similar in shape/flatness and showed increasing effect (area under the curve for GIR: AUC–GIRtotal) with increasing dose [low dose: 647 ± 580, 882 ± 634, 571 ± 647 mg/kg (insulin detemir vs. NN344 vs. insulin glargine]; medium dose: 1203 ± 816, 1720 ± 1109, 1393 ± 1203 mg/kg and high dose: 2171 ± 1344, 3119 ± 1549, 2952 ± 2028 mg/kg; p = 0.48]. The duration of action increased with rising doses of all insulin preparations, without major differences between treatments. BG remained below 7 mmol/l in nearly all the experiments. Within‐subject variability was lower for the albumin‐bound insulin analogues, insulin detemir and NN344, than for insulin glargine (p < 0.0001). Between‐subject variability did not differ between treatments, nor did the effects on BG, C‐peptide, FFA, EGP or PGU.Conclusions:  In individuals with type 2 diabetes, the time‐action profiles and the duration of action of the albumin‐bound insulin analogues, insulin detemir and NN344, were comparable with those of insulin glargine, whereas within‐subject variability in the metabolic effect was significantly lower. Therefore, insulin detemir and NN344 seem to be as well suited as insulin glargine for once‐daily administration in type 2 diabetes. The better predictability may be an important characteristic of the albumin‐bound analogues as insulin detemir has already been shown to improve hypoglycaemia.

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Thông tin xuất bản

Diabetes, Obesity and Metabolism

Tập 9 Số 3

290-299

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