BACKGROUND: The variability of the metabolic action of insulin after subcutaneous (sc) injection hampers optimal insulin therapy. Insulin formulations with a reduced tendency to form hexamers might exhibit a reduced variability of absorption from the sc insulin depot into the blood stream. METHODS: We investigated the within-subject variability of pharmacodynamic and pharmacokinetic properties of an ultra-fast insulin (UFI) formulation and regular human insulin (RHI) in patients with type 1 diabetes. Fourteen patients participated in six 10-hour euglycemic glucose clamp experiments. In this double-blind, crossover study, subjects were randomly assigned to a sequence of two experimental blocks: each block consisted of three doses of 0.1 IU/kg UFI or RHI, respectively, administered on separate days by abdominal sc injection. RESULTS: Ultra-fast insulin has an earlier onset of action and shorter time to maximal plasma insulin concentration when compared to RHI (tGIR(max) 99 +/- 36 min vs. 154 +/- 74 min, p = 0.002; tC(max) 33 +/- 16 min vs. 97 +/- 39 min, p = 0.00001). The within-subject variability of plasma insulin tC(max) (p = 0.027) and of tGIR(max) (p = 0.022) was less for UFI than for RHI. CONCLUSIONS: In patients with type 1 diabetes, this UFI showed reduced within-subject variability when compared with RHI.
RCT Entities:
BACKGROUND: The variability of the metabolic action of insulin after subcutaneous (sc) injection hampers optimal insulin therapy. Insulin formulations with a reduced tendency to form hexamers might exhibit a reduced variability of absorption from the sc insulin depot into the blood stream. METHODS: We investigated the within-subject variability of pharmacodynamic and pharmacokinetic properties of an ultra-fast insulin (UFI) formulation and regular humaninsulin (RHI) in patients with type 1 diabetes. Fourteen patients participated in six 10-hour euglycemic glucose clamp experiments. In this double-blind, crossover study, subjects were randomly assigned to a sequence of two experimental blocks: each block consisted of three doses of 0.1 IU/kg UFI or RHI, respectively, administered on separate days by abdominal sc injection. RESULTS: Ultra-fast insulin has an earlier onset of action and shorter time to maximal plasma insulin concentration when compared to RHI (tGIR(max) 99 +/- 36 min vs. 154 +/- 74 min, p = 0.002; tC(max) 33 +/- 16 min vs. 97 +/- 39 min, p = 0.00001). The within-subject variability of plasma insulin tC(max) (p = 0.027) and of tGIR(max) (p = 0.022) was less for UFI than for RHI. CONCLUSIONS: In patients with type 1 diabetes, this UFI showed reduced within-subject variability when compared with RHI.
Authors: S Steiner; M Hompesch; R Pohl; P Simms; F Flacke; T Mohr; A Pfützner; L Heinemann Journal: Diabetologia Date: 2008-07-19 Impact factor: 10.122