Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Aim To investigate the mechanisms behind the lower postprandial glucose (PPG) concentrations achieved with fast‐acting insulin aspart (faster aspart) than with insulin aspart (IAsp). Materials and methods In a randomized, double‐blind, crossover trial, 41 people with type 1 diabetes received identical subcutaneous single faster aspart and IAsp doses (individualized for each participant), together with a standardized mixed meal (including 75 g carbohydrate labelled with [1‐ 13 C] glucose). PPG turnover was determined by the triple‐tracer meal method using continuous, variable [6‐ 3 H] glucose and [6,6‐ 2 H 2 ] glucose infusion. Results Insulin exposure within the first hour was 32% greater with faster aspart than with IAsp (treatment ratio faster aspart/IAsp 1.32 [95% confidence interval {CI} 1.18;1.48]; P < .001), leading to a 0.59‐mmol/L non‐significantly smaller PPG increment at 1 hour (ΔPG 1h ; treatment difference faster aspart–IAsp −0.59 mmol/L [95% CI –1.19; 0.01]; P = .055). The trend towards reduced ΔPG 1h with faster aspart was attributable to 12% greater suppression of endogenous glucose production (EGP; treatment ratio 1.12 [95% CI 1.01; 1.25]; P = .040) and 23% higher glucose disappearance (1.23 [95% CI 1.05; 1.45]; P = .012) with faster aspart than with IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster aspart than for IAsp (1.36 [95% CI 1.01;1.88]; P = .042). Conclusions The trend towards improved PPG control with faster aspart vs IAsp in this study was attributable to both greater early suppression of EGP and stimulation of glucose disappearance.