A New Highly Concentrated Insulin Aspart AT278 (500&#x2009;U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

Eva Svehlikova; Christina Gatschelhofer; Bettina Lackner; Maria Ratzer; Gabriele Fluhr; Anja Stoisser; Gregor Kolaric; David Gerring; Sarah Howell; Jan Jezek; Fiona Lawrence; Thomas R Pieber

doi:10.1111/dom.71150

PubMed · 42530378

A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

Eva Svehlikova·Christina Gatschelhofer·Bettina Lackner·Maria Ratzer·Gabriele Fluhr·Anja Stoisser·Gregor Kolaric·David Gerring·Sarah Howell·Jan Jezek·Fiona Lawrence·Thomas R Pieber

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Abstract

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500 U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100 U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500 IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7 kg/m2) receiving a single subcutaneous dose (0.5 U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9 min vs. 35 min vs. 55 min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7 kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p < 0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

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Eva Svehlikova, Christina Gatschelhofer, Bettina Lackner, Maria Ratzer, Gabriele Fluhr, Anja Stoisser, Gregor Kolaric, David Gerring, Sarah Howell, Jan Jezek, Fiona Lawrence, Thomas R Pieber. 2026-07-30. A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.. https://doi.org/10.1111/dom.71150

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Journal Article; Randomized Controlled Trial resource Adult subject Aged subject Blood Glucose subject Body Mass Index subject Cross-Over Studies subject Diabetes Mellitus, Type 2 subject Double-Blind Method subject Female subject Humans subject Journal Article subject Male subject Middle Aged subject Obesity subject Overweight subject Randomized controlled trials study

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