A Multicenter Randomized Trial Evaluating Fast-Acting Insulin Aspart in the Bionic Pancreas in Adults with Type 1 Diabetes

Objective: To evaluate the insulin-only configuration of the iLet((R)) bionic pancreas (BP) using fast-acting insulin aspart (Fiasp((R))) in adults with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized trial, 275 adults with T1D (18-83 years old, baseline HbA1c 5.3%-14.9%) were randomly assigned 2:2:1 to use the BP with fast-acting insulin aspart (BP-F group, N=114), BP with aspart or lispro (BP-A/L group, N=107), or a control group using their standard-care insulin delivery (SC group, N=54) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. The BP-F versus SC comparison was considered primary and BP-F versus BP-A/L secondary. Results: Meanstandard deviation (SD) HbA1c decreased from 7.8%1.2% at baseline to 7.1%+/- 0.6% at 13 weeks with BP-F versus 7.6%+/- 1.2% to 7.5%+/- 0.9% with SC (adjusted difference=-0.5%, 95% CI -0.7 to -0.3, P<0.001). CGM-measured percent time <54mg/dL over 13 weeks with BP-F was noninferior to SC (adjusted difference=0.00%, 95% CI -0.07 to 0.05, P<0.001 for noninferiority based on a prespecified noninferiority limit of 1%). Over 13 weeks, mean time in range 70-180mg/dL (TIR) increased by 14% (3.4h/day) and mean CGM glucose was reduced by 18mg/dL with BP-F compared with SC (P<0.001). Analyses of time >180mg/dL, time >250mg/dL, and the SD of CGM glucose all favored BP-F compared with SC (P<0.001). Differences between BP-F and BP-A/L were minimal, with no difference in HbA1c at 13 weeks (adjusted difference=-0.0%, 95% CI -0.2 to 0.1, P=0.67) or mean glucose (adjusted difference=-2.0mg/dL, 95% CI -4.3 to 0.4, P=0.10). Mean TIR was 2% greater with BP-F than BP-A/L (95% CI 1 to 4, P=0.005), but the percentages of participants improving TIR by >= 5% were not significantly different (P=0.49) and there were no significant differences comparing BP-F versus BP-A/L across nine patient-reported outcome surveys. The rate of severe hypoglycemia events did not differ among the three groups. Conclusions: In adults with T1D, HbA1c was improved with the BP using fast-acting insulin aspart compared with standard care without increasing CGM-measured hypoglycemia. However, the effect was no better than the reduction observed with the BP using aspart or lispro.

Automated summary

The insulin-only configuration of the iLet((R)) bionic pancreas with fast-acting insulin aspart showed improvement in HbA1c without increasing the risk of hypoglycemia in adults with type 1 diabetes.