Fast‐acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose‐lowering effect compared with insulin aspart

摘要

Abstract Aims To investigate the pharmacokinetic/pharmacodynamic properties of fast‐acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in people with type 2 diabetes (T2D). Materials and methods In a randomized, double‐blind, crossover design, 61 people with T2D usually treated with insulin?±?oral antidiabetic drug(s) received single‐dose faster aspart and IAsp (0.3 U/kg) on separate visits. Blood samples for pharmacokinetic assessment were collected frequently until 12?hours post‐dose. Glucose‐lowering effect was determined in a euglycaemic clamp lasting up to 12?hours post‐dose (target 5.0 mmol/L). Results The serum IAsp pharmacokinetic profile and glucose‐lowering effect profile were shifted to the left for faster aspart versus IAsp. Least squares mean (± SE) onset of appearance was 3.3?±?0.3 minutes for faster aspart, which was 1.2 minutes earlier than for IAsp (95% confidence interval [CI] ?1.8;?0.5; P ?=?.001). Onset of action for faster aspart was 8.9 minutes earlier (95% CI ?12.1;?5.7; P ??.001) than for IAsp. During the first 30?minutes after dosing, 89% larger IAsp exposure (ratio faster aspart/IAsp 1.89 [95% CI 1.56;2.28]; P ??.001) and 147% greater glucose‐lowering effect (2.47 [95% CI 1.58;6.22]; P ??.001) were observed for faster aspart compared with IAsp. Offset of exposure (time to 50% of maximum IAsp concentration in the late part of the pharmacokinetic profile) occurred earlier for faster aspart (difference faster aspart – IAsp ?36.4 minutes [95% CI ?55.3;?17.6]; P ??.001). The treatment difference of faster aspart – IAsp in offset of glucose‐lowering effect (time to 50% of maximum glucose infusion rate in the late part of the glucose infusion rate profile) was ?14.4 minutes (95% CI ?34.4;5.5; P ?=?.152). Conclusions In people with T2D, faster aspart was associated with earlier onset and greater initial exposure and glucose‐lowering effect compared with IAsp, as previously shown in people with type 1 diabetes.