Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial

Abstract

Background: The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity.

Methods: We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2-11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220.

Findings: We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7-1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study.

Interpretation: Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas.

Funding: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

Figure 1

Trial profile

Figure 2. Distributions of the mean continuous glucose monitoring glucose concentration and hypoglycaemia, and cumulative continuous glucose monitoring glucose concentrations

(A) Mean CGM glucose concentration in each participant on days 2–11 of the comparator period (centre of red circles), connected by a line to the corresponding mean CGM glucose concentration during the bionic pancreas period (centre of black circles). The diameter of each circle is proportional to the percentage of time that the patient spent with a CGM glucose concentration less than 3·3 mmol/L. The solid red line represents the aggregate mean for all study participants. The dashed horizontal red line shows a mean CGM glucose concentration of 8·6 mmol/L. (B) Cumulative CGM glucose concentrations during the bionic pancreas period (day land days 2–11) and during the 11-day comparator period, and (C) corresponding cumulative night-time CGM glucose concentrations. In (B) and (C), the shaded regions correspond to CGM glucose concentrations less than 2·8 mmol/L (red), 3·9–6·7 mmol/L (green), and 67–10·0 mmol/L (blue). CGM=continuous glucose monitoring.

Figure 3. Variation of the instantaneous mean continuous glucose monitoring glucose concentration

Daily mean CGM glucose concentrations and percentages of time with CGM glucose concentration less than 3·3 mmol/L over 11 days during the full study period (A) and during the night-time period (B). CGM=continuous glucose monitoring.

Figure 4. Distributions of mean continuous glucose monitoring glucose concentrations and insulin doses

(A) Distribution of the mean CGM glucose concentrations per participant during the bionic pancreas and comparator periods with mean CGM glucose concentrations on days 2–11 divided into intervals of 0·39 mmol/L. The dashed red line shows a mean glucose concentration of 8·6 mmol/L. (B) Distribution of total daily doses of insulin, divided into intervals of 0·1 U/kg of body mass per day. CGM=continuous glucose monitoring.