Evaluation of early postprandial suppression of EGP with faster aspart vs aspart

Background and aims: fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with added excipients providing faster early absorption and improved postprandial glucose (PPG) control. This randomised, double‑blind, crossover trial investigated mechanisms behind the lower PPG seen with faster aspart versus IAsp. Method: subjects with T1D (n=40; HbA1c 7.3±0.7%) received identical doses of faster aspart and IAsp (individualised by subject; 0.06–0.28 U/kg subcutaneously) at the start of a standardised mixed meal (75 g carbohydrate labelled with [1-13C] glucose). PPG turnover was assessed by the triple-tracer meal method using continuous, variable [6-3H] glucose and [6,6-2H2] glucose infusion. Results: early insulin exposure was greater for faster aspart versus IAsp (AUCIAsp,0–30min treatment ratio [95% CI] 1.93 [1.59;2.34]; AUCIAsp,0–1h 1.32 [1.18;1.48], both p<0.001), leading to smaller PPG increment at 1 h (ΔPG1h treatment difference [95% CI] −10.6 [−21.5;0.3] mg/dL, p=0.055). The smaller ΔPG1h with faster aspart was due to greater suppression of endogenous glucose production (EGPsuppression,0–30min 1.96 [1.13;4.43], p=0.017; EGPsuppression,0–1h 1.12 [1.01;1.25], p=0.040) and higher glucose disappearance (ΔAUCRd,0–1h 1.23 [1.05;1.45]; p=0.012) with faster aspart versus IAsp during the first hour post-dose. Suppression of free fatty acid levels was greater for faster aspart versus IAsp (AOCFFA,0–1h 1.36 [1.01;1.88], p=0.042). Conclusion: faster aspart provides improved PPG control versus IAsp partly through earlier and greater EGP suppression.