Fully closed-loop control with ultra-rapid versus standard insulin lispro: A randomised crossover study simulating missed meal boluses

Abstract

Aims

Ultra-rapid insulin lispro (URIL) is associated with faster insulin absorption and earlier offset than standard insulin lispro (IL). This study evaluated whether URIL improves glucose control in a fully closed-loop setting over an 8-h period compared to IL under conditions simulating a missed meal bolus.

Methods

In this open-label, randomised crossover trial, 18 adults with type 1 diabetes using insulin pump therapy [12 females, age 39.1 (14.2) yrs., HbA1c 57.9 (8.7) mmol/mol] completed two 8-h inpatient sessions (09:00 to 17:00 h). Glucose levels were managed using the CamAPS FX closed-loop system with either URIL or IL, in random order. Participants received a standardised meal at 11:00 h without a meal bolus. The primary endpoint was the percentage of time in range (TIR; 3.9–10 mmol/L) based on sensor glucose.

Results

Data related to the 8-h study period from 17 participants were analysed. TIR was numerically higher but not statistically significant with URIL than IL [49.3 (15.6) vs. 39.9 (18.9)%; p = 0.072], with lower time spent in Level 1 (>10 mM) [50.7 (15.6) vs. 59.5 (19.1)%; p = 0.098] and Level 2 hyperglycaemia (>13.9) [18.7 (17.1) vs. 27.9 (19.8)%; p = 0.136]. Similar trends were observed in the 4-h post-meal period. Time in hypoglycaemia was low and comparable between both periods (p > 0.05).

Conclusion

URIL in a fully closed-loop setting showed a clinically meaningful trend towards improved TIR and reduced hyperglycaemia compared to IL. Further advancements in faster-acting insulins are needed to alleviate the burden of pre-meal bolusing and enhance fully closed-loop performance in the future.