Identification and comparison of insulin pharmacokinetics injected with a new 4-mm needle vs 6- and 8-mm needles accounting for endogenous insulin and C-peptide secretion kinetics in non-diabetic adult males.

Abstract

Many patients with diabetes now use 5-, 6- or 8-mm needles for insulin injection. However, it is unclear whether needle length, particularly for shorter needles, affects the pharmacokinetic properties of insulin. This was a three-way, randomized, cross-over, single-center study involving 12 healthy Japanese adult males (age 27.4±4.14years; weight 64.2±5.2kg; body fat percentage 18.2±1.5%). Participants received a subcutaneous (abdomen) dose of insulin lispro (1.5U for participants weighing 55 to <65.0kg; 2.0U for participants weighing 65.0 to <80.0kg) delivered using a 32-G×4mm (32G×4), 31-G×8mm (31G×8) or 32-G×6mm (32G×6) needle with a 3-7-day washout between doses. Pharmacokinetic parameters of exogenous insulin were identified using non-linear least squares, where the total insulin concentration was fit to the measured plasma insulin concentration using an overall combined model that accounted for C-peptide/insulin secretion in addition to the injected dose. Maximum concentration and area under the curve for 0 to infinity min for insulin were bioequivalent for the 32G×4 needle relative to the 32G×6 and the 31G×8 needles. The time to the maximum insulin concentration was bioequivalent for the 32G×4 needle relative to the 32G×6 needle, but not the 31G×8 needle. The use of 4-mm needles is unlikely to change the pharmacokinetic properties of insulin when injected subcutaneously in adults. This trial was registered with UMIN-CTR (no. UMIN000004469).