Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogues in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective To evaluate postprandial glucose control when applying (i)faster-acting insulin aspart (Fiasp) compared to insulin aspart, and (ii)ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro (NCT04055480,NCT05257460). Endpoints included incremental area under curve iAUC-2h, iAUC-4h, 4h postprandial time in target range, time above range, and time below range. Results Two trials with 8-weeks of data from 51 adults with type 1 diabetes were analysed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2h (95%CI 56 to 127); p<0.001 and 151 mmol/L per 4h (95%CI 74 to 229); p<0.001, respectively) and evening (p<0.001 and p=0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4h postprandially significantly increased during Lyumjev with a mean difference of 6.7percentage points (95%CI 3.3 to 10) and 5.7percentage points (95%CI 1.4 to 9.9) for breakfast and evening, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (p>0.05). Conclusion The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart.