Dual Hormone Bionic Pancreas vs Standard Care

January 17, 2017
Veronica Hackethal, MD

The device, initialized using only body mass, with no required data on usual insulin regimens, was compared to standard care with insulin pump and CGM.

A dual hormone bionic pancreas that delivers insulin and glucagon via an automated algorithm run by a smart phone app improves glycemic control better than standard care in the home setting in adults with T1DM, according to a study published online in the Lancet.1

“Use of the bihormonal bionic pancreas was associated with a mean glucose concentration predicted to correspond to a glycated haemoglobin of 7% or lower in 92% of participants versus 41% in those in the usual care comparator period, while simultaneously reducing hypoglycaemia to 0.6% of the time versus 1.9% of the time in the comparator period,” wrote first author Firas El-Khatib, PhD, of Boston University (Boston, MA), and colleagues.

Past studies from this group have found that this type of artificial pancreas significantly decreases glucose concentrations and hypoglycemia over five days in children in a diabetes camp setting, and in adults in a hotel setting.2,3

The device tested in the new study may provide an easier, more practical way for patients to control their T1DM. It was initiated autonomously using only participants’ body mass, and did not require carbohydrate counting or data on participants’ past insulin requirements. Two other studies have shown the feasibility of using the dual hormone bionic pancreas in the home setting, but these devices required adjustment of the algorithm by the research team.4,5

The randomized, crossover study included participants with T1DM and aged at least 18 years. Participants were already on insulin pump therapy and lived within 30 minutes’ drive of four US study sites:  Massachusetts General Hospital (Boston, MA); University of Massachusetts Medical School (Worcester, MA); Stanford University (Palo Alto, CA); and the University of North Carolina Chapel Hill (Chapel Hill, NC). 

Researchers randomized participants to the dual hormone bionic pancreas (which delivers insulin and glucagon) or usual care (participant’s own insulin pump and continuous glucose monitor [CGM], if they used one). After 11 days, participants switched groups, with the bionic pancreas group switching to usual care, and vice versa for the usual care group. Participants remained at home and continued normal daily activities throughout the study.

The bionic pancreas consists of an iPhone 4S connected to a CGM. Insulin and glucagon dosing algorithms run as an app on the iPhone, and use data from CGMs to control delivery of insulin and glucagon. The device was initialized using only the participant’s body mass, and did not require data on participants’ usual insulin regimens. Participants used the device without restrictions on diet or exercise, and without the requirement for carbohydrate counting.

The app included an optional meal announcement, which participants could use to label the main meals of the day as “typical,” “more than typical,” “less than typical,” or “a small bite.” This feature triggered a partial insulin bolus adapted to the meal type and size, decreasing the need for insulin titration at meals. Researchers encouraged but did not require participants to use this feature before meals.

Participants were remotely monitored to detect when the device was disconnected for over 15 minutes, and for severe hypoglycemia. Thirty-nine participants completed the study, and were included in the analysis.

Key Results:

• Hyperglycemia: Improved with the bionic pancreas vs standard care

♦ Mean CGM glucose concentration: 7.8 mmol/L vs 9.0 mmol/L, respectively, P<0·0001

• Hypoglycemia: Improved with the bionic pancreas vs standard care

♦ Mean time spent in hypoglycemia: 0.6% vs 1·9%, respectively P<0·0001

♦ Symptomatic hypoglycemia, number of times carbohydrates needed per day, and grams of rescue carbohydrates needed per day significantly decreased (P=0.023, P<0.0001, P=0.00033, respectively)

• Significantly increased nausea and mean total daily insulin dose with the bionic pancreas vs standard care (P=0.0024 and P=0.014, respectively)

• No reports of serious adverse events

The authors noted that the increase in insulin amount with the bionic pancreas relative to standard care was small and may have been due to inadequate amounts of insulin used in standard care. They also noted that insulin requirements varied widely, yet the bionic pancreas was able to adapt automatically to meet participants’ needs.

They noted several limitations, including the short study duration, and small number of participants with better than usual glycemic control. Use of the bionic pancreas required daily reconstitution and replacement of glucagon. Though stable formulations have now been developed, cost increases of adding glucagon remain unknown.

They concluded: “A bihormonal bionic pancreas has the potential to deliver substantially improved glycaemic management in patients with type 1 diabetes. Since only the body mass is required for initialisation of the system, less time and effort will be needed of health-care providers to start treatment. Since meal announcements are optional and no carbohydrate counting is required, use of the bionic pancreas reduces the patient burden associated with management of diabetes.”

In a linked editorial, Helen Murphy, MD (University of East Anglia, Norwich, UK) and Zoe Stewart, MD, PhD  (University of Cambridge, Cambridge, UK) highlighted the remarkable progress in developing various versions of an artificial pancreas (insulin-only and insulin plus glucagon devices). Results from trials on these devices have been “consistently positive,” they wrote.6

“As the focus now moves towards commercialization and real-world application of both types of automated insulin delivery systems, a key milestone of 2016 was the US Food and Drug Administration approval of a commercially available automated insulin-only delivery system, the Medtronic Minimed 670G (Dublin, Ireland),” they added.

They noted that larger, longer term clinical trials are needed. These need to be conducted in real-life situations, and include patients who are new to using advanced diabetes technology such as insulin pumps.

“With patient demand for open-source control algorithms linking insulin delivery to real-time continuous glucose concentrations increasing, research must keep pace so that new technologies are available to suitable candidates without them having to resort to potentially unsafe alternatives,” they emphasized.

Take-home Points

• A dual hormone bionic pancreas that delivers insulin and glucagon via an automated algorithm run by a smart phone app improves glycemic control and decreases hypoglycemia compared to standard care in the home setting in adults with T1DM.

• The device was initialized using only the participant’s body mass, did not require data on usual insulin regimens, and had a meal-time partial insulin bolus feature that decreases the need for insulin titration at meals.

• Participants used the device without restrictions on diet or exercise, and without the requirement for carbohydrate counting.

• Larger, longer-term trials are needed.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

One or more authors reports equity, research and technical support, lecture fees, board of director or scientific advisory board membershipXXX in one or more of the following: Beta Bionics, Dexcom, Tandem Diabetes Care, Eli Lilly, Abbott Diabetes Care and/or Companion Medical.

Drs. El-Khatib and Damiano hold a patent related to an artificial pancreas for type 1 diabetes, and pending patent applications related to a blood glucose control system, all assigned to Boston University.

Dr. Russell has a pending patent application for a blood glucose control system, assigned to Partners HealthCare and Massachusetts General Hospital.

References:

1. El-Khatib FH, et al. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2016 Dec 20.

2. Russell SJ, et al. Outpatient glycemic control with a bionic pancreas in type 1 diabetes. N Engl J Med 2014;371:313-325.

3. Russell SJ, et al. Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial. Lancet Diabetes Endocrinol. 2016;4:233-243.

4. van Bon AC, et al. Feasibility of a portable bihormonal closed-loop system to control glucose excursions at home under free-living conditions for 48 hours. Diabetes Tech Ther 2014;16:131-136.

5. Blauw H, et al. Performance and safety of an integrated bihormonal artificial pancreas for fully automated glucose control at home. Diabetes Obes Metab 2016;18:671-677.

6. Murphy HR, Stewart ZA. Automated insulin delivery: what’s new, needed, and next? Lancet. 2016 Dec 20.

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