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

Abstract

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using fast-acting insulin aspart (Fiasp®) 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: Mean ± standard 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 <54 mg/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 70-180 mg/dL (TIR) increased by 14% (3.4 h/day) and mean CGM glucose was reduced by 18 mg/dL with BP-F compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/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 = -2.0 mg/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. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Keywords: Adult; Artificial pancreas; Automated insulin delivery; Bionic pancreas; Evaluation; Fast-acting insulin; Type 1 diabetes.

Conflict of interest statement

Dr. Beck reports no personal financial disclosures but reports that his institution has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Eli Lilly and Novo Nordisk; and consulting fees from Insulet, Bigfoot Biomedical, vTv Therapeutics, and Diasome.

Dr. Russell has issued patents and pending patents on aspects of the bionic pancreas that are assigned to Massachusetts General Hospital and licensed to Beta Bionics, has received honoraria and/or travel expenses for lectures from Novo Nordisk, Roche, and Ascensia, serves on the scientific advisory boards of Unomedical, served on scientific advisory board and had stock in Companion Medical that was bought out by Medtronic, has received consulting fees from Beta Bionics, Novo Nordisk, Senseonics, and Flexion Therapeutics, has received grant support from Zealand Pharma, Novo Nordisk, and Beta Bionics, and has received in-kind support in the form of technical support and/or donation of materials from Zealand Pharma, Ascencia, Senseonics, Adocia, and Tandem Diabetes.

Dr. Damiano has issued patents and pending patents on aspects of the bionic pancreas, and is an employee, the Executive Chair of the Board of Directors, and shareholder of Beta Bionics. Dr. El-Khatib has issued patents and pending patents on aspects of the bionic pancreas and is an employee and shareholder of Beta Bionics. Ms. Ruedy has no personal financial disclosures but reports that her employer has received grant support from Beta Bionics, Dexcom and Tandem Diabetes Care. Ms. Balliro reports receiving consulting payments from Beta Bionics, Novo Nordisk and Zealand Pharma. Ms. Li has no personal financial disclosures but reports that her employer has received grant support from Beta Bionics, Dexcom and Tandem Diabetes Care. Dr. Calhoun is a former Dexcom employee and his current employer has received consulting payments on his behalf from vTv Therapeutics, Beta Bionics, Dexcom, and Diasome.

Figures

FIG. 1.

HbA1c at 13 Weeks. (A) Cumulative distribution of HbA1c at 13 weeks (N = 53 SC, 111 BP-F, 102 BP-A/L). (B) Scatterplot of HbA1c (%) at 13 weeks versus baseline (N = 52 SC, 111 BP-F, 102 BP-A/L). BP-A/L, BP with aspart or lispro; BP-F, BP with fast-acting insulin aspart; SC, standard care.

FIG. 2.

Time (A) Boxplots of % time <54 mg/dL (N = 54 SC, 114 BP-F, 107 BP-A/L). Black dots indicate the mean values, horizontal bars in the boxes indicate the medians, and the bottom and top of each box represent the 25th and 75th percentiles, respectively. (B) Scatterplot of % time <54 mg/dL at 13 weeks versus baseline (N = 54 SC, 113 BP-F, 106 BP-A/L).

FIG. 3.

Mean glucose by hour over the 24-h day. (A) BP-F group versus SC group. (B) BP-F group versus BP-A/L group. Dots and solid lines represent the medians, colored area reflects the interquartile range (extending to 25th and 75th percentiles), and dashed lines represent the 10th and 90th percentiles.

FIG. 4.

Scatterplot of mean glucose at 13 weeks versus baseline (N = 54 SC, 113 BP-F, 106 BP-A/L).

FIG. 5.

Time in range 70–180 mg/dL (N = 54 SC, 113 BP-F, 106 BP-A/L). (A) Cumulative distribution of % time 70–180 mg/dL at 13 weeks. (B) Scatterplot of % time in range 70–180 mg/dL at 13 weeks versus baseline.