Coming Soon: 'Artificial Pancreas' Options for Diabetes
Miriam E Tucker
June 20, 2016
NEW ORLEANS — Nearly closed-loop systems (also referred to as an "artificial pancreas") for improving glycemic control and minimizing hypoglycemia in type 1 diabetes are advancing rapidly, including iterations that deliver insulin alone, insulin with glucagon, or glucagon alone.
Findings for several of the products in development demonstrating improvements in glycemic control and reductions in hypoglycemia were presented here at the American Diabetes Association (ADA) 2016 Scientific Sessions.
"Some people may do well on insulin only, while others may need glucagon," Vincent Crabtree, PhD, director of the artificial pancreas program at JDRF, in New York, told Medscape Medical News, adding, "JDRF would like people to have choice, and we'd like all to be covered [by payers]."
The insulin-only hybrid closed-loop 670G system (Medtronic MiniMed) is the furthest along in development, and pivotal trial results were presented during a late-breaking poster session. Premarket approval submission with the US Food and Drug Administration is anticipated this summer.
Not far behind is the "bionic pancreas," a term originally coined by Boston University biomedical engineering professor Edward R Damiano, PhD, and colleagues for their system that dispenses both insulin and glucagon. Now a fully integrated dual-chamber device called the iLet, it is being further developed by Beta Bionics, a public-benefit corporation that Dr Damiano recently cofounded.
Dr Vincent Crabtree
Data presented at the meeting for the iLet included its use as a single-hormone device, with insulin only and glucagon only, as well as its dual-chamber use.
Beta Bionics is working with Denmark-based Zealand Pharma to develop a more stable glucagon analog for use with the iLet, as the current formulation requires daily reconstitution. Because the regulatory pathway for that product is expected to take some time, the iLet device is likely to reach the market sooner with single-chamber indications, Laya Ekhlaspour, MD, a pediatric endocrinology fellow at Massachusetts General Hospital in Boston, explained.
"Waiting for approval of a more stable glucagon could delay this coming to market....We plan to start our pivotal study with an insulin-only version to get approval faster," Dr Ekhlaspour, who presented the iLet insulin-alone data at the meeting, told Medscape Medical News.
Courtney Balliro, RN, CDE, also at Massachusetts General Hospital, who presented the glucagon-only data, noted, "Creating a new drug takes a lot longer. We believe glucagon is necessary [in a closed-loop system], but we can help people in the meantime."
Indeed, Dr Crabtree said, "We don't know what's going to happen. We don't know if there will be a stable glucagon or if insurers will pay for it. So at the very minimum we need an insulin-only system."
He added that several other companies are also moving toward closed-loop systems, many with JDRF funding.
Hybrid Closed-Loop System ― First on Market by Year End?
The Medtronic 670G is a hybrid closed-loop system, meaning that the user must periodically calibrate it and give mealtime and correction insulin boluses as needed, while it takes care of background insulin delivery. The system consists of Medtronic's insulin pump, a fourth-generation continuous-glucose sensor, and a control algorithm.
In the pivotal study, reported as a late-breaking poster by Richard Bergenstal, MD, of Park Nicollet Methodist Hospital, in St Louis Park, Minnesota, 124 adolescent and adult patients with type 1 diabetes wore the hybrid closed-loop system, first for 6 days in a supervised hotel setting followed by 3 months at home.
While using the 670G, patients spent 24.5% of the time with sensor glucose values above 180 mg/dL compared with 27.4% of the time at baseline (P < .001); equivalent figures were 3.3% vs 5.9% for glucose below 70 mg/dL (P < .001) and 0.6% vs 1.0% for glucose at or below 50 mg/dL (P < .001).
Very similar results were seen for sensor values between 10:00 pm and 7:00 am (all P < .001).
None of the patients developed diabetic ketoacidosis, severe hypoglycemia, or serious device-related adverse events during 12,389 patient-days. After the study ended, 99 patients entered a program that allowed them to continue using the system.
"Our hybrid closed-loop system is designed to automate the delivery of insulin and has undergone rigorous evaluation in the largest and longest at-home closed-loop study....We are the first company to complete a pivotal trial on artificial-pancreas technology and will be filing a premarket approval submission to the FDA in the coming weeks," study coauthor Francine R Kaufman, MD, vice president of Global Medical Affairs for Medtronic Diabetes, Los Angeles, California, said in a statement to Medscape Medical News.
Glucagon-Only Delivery
Dr Courtney Balliro
Meanwhile, Ms Balliro presented her data on the closed-loop glucagon-only system during the ADA president's oral abstract session. Here, with only the glucagon chamber filled, the iLet delivers very small doses of glucagon in response to sensor-detected hypoglycemia.
In the double-blind, placebo-controlled, crossover study, 22 adults with type 1 diabetes with reduced hypoglycemia awareness were randomized to glucagon (mean dose 0.5 mg/day, about half the usual rescue dose) or placebo, along with using their own insulin pumps or multiple daily insulin injections, for 7 days.
Overall, there was a 75% reduction in time spent in hypoglycemia (< 60 mg/dL), 1.2% with the glucagon system vs 4.7% with placebo (P < .0001). Nocturnal hypoglycemia was reduced by 91% to just 0.5% from 5.4% with placebo (P < .0001).
At the same time, there was no increase in mean glucose levels recorded by the continuous-glucose monitor (153 vs 152 mg/dL, P = .60), nor did patients report excess nausea, vomiting, headache, or skin infections on glucagon days.
"The glucagon was tolerated very well," Ms Balliro noted.
In addition to pursuing the glucagon-delivery system as a stand-alone and ― as part of the dual-hormone device for people with diabetes ― the group also plans to study the glucagon-alone system in people with conditions for which they would not require insulin delivery, including postbariatric surgery hypoglycemia or congenital hyperinsulinism.
"We're looking to expand our research to include those folks, too," she concluded.
Insulin-Only System, With Slightly Higher Glucose Targets
Dr Laya Ekhlaspour
Dr Ekhlaspour presented findings from a random-order crossover iLet study in 20 adults with type 1 diabetes. The study compared six 3-day arms: two insulin-only configurations of the device (glucose targets of 130 and 145 mg/dL) with a bihormonal configuration (glucose targets of 100, 115, or 130 mg/dL) and usual care (patient-managed insulin-pump therapy). Glucose targets were set higher for the insulin-only configuration, to minimize the risk of hypoglycemia when glucagon was not present.
Study patients carried out their usual daily routines with no restrictions on food or exercise during each test period.
Mean glucose was higher for the insulin-only pump group for the 145 mg/dL vs the 130 mg/dL target with configuration, or for usual care (P < .0001 to .034), but there were no significant differences among groups in time spent with blood glucose below 60 mg/dL (all P > .28).
The Boston team is currently comparing the insulin-only and bihormonal configurations with a target glucose of 110 mg/dL, Dr Ekhlaspour said.
Bionic Pancreas: As Little Patient Involvement As Possible
Dr Damiano presented data from a multicenter study in 39 patients who wore the dual-hormone 'bionic pancreas' system for 11 days at home with no restrictions on food or activity.
As he reported last year at the American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress, mean glucose levels were lower with the dual-hormone iLet compared with standard pump therapy (141 vs 162 mg/dL; P < .0001), and time spent in hypoglycemia (< 60 mg/dL) was reduced with the dual-hormone iLet (0.6% vs 1.9%; P < .0001).
Over the study period, the iLet was associated with a reduction in mean number of symptomatic hypoglycemia events per day (0.59 vs 0.90; P = 0.023).
Dr Damiano explained that the dual-hormone iLet differs from the Medtronic system in the degree of patient input required. For the iLet, the person simply inputs their body weight and the device essentially takes over, whereas the Medtronic 670G still requires the user to count carbs, take an insulin bolus before meals, and program their insulin doses.
The "bionic pancreas" also has an optional meal announcement, whereby the person simply inputs whether an upcoming meal is bigger, smaller, or about the same size as usual. But the system will compensate even if the person forgets to do that, he said during a press briefing.
"The device is designed to involve as little involvement from the patient as possible....It doesn't care about your skill set," he commented.
Coming Soon
Dr Edward Damiano
At least two other companies, Tandem and Bigfoot Biomedical, have also announced late-stage testing of partially closed-loop systems.
"Remember what the first cellphones were like. Things get better over time, and this is part of the natural technology evolution....So in a few years there will be several to choose from. You'll be able to choose based on the pros and cons of each," Dr Crabtree said.
He cautioned, though, that the cost of glucagon for the iLet could present an obstacle.
"We don't know what's going to happen to the healthcare system in the future. It may be that you can get an insulin-only system with your insurance and if you want glucagon you have to pay out of pocket. Or maybe [the healthcare system] will pay for glucagon but only if the physician says you need a glucagon system," such as for people with hypoglycemic unawareness or who exercise frequently.
In all, he said, "Each person's diabetes is unique....Just one type of system won't work for everybody. It's better to have the choice."
Dr Crabtree is an employee of the JDRF, which funds several companies involved in closed-loop system development. Dr Damiano is cofounder and shareholder of Beta Bionics. Ms Balliro and Dr Ekhlaspour have reported no relevant financial relationships. Dr Bergenstal receives research support from Medtronic. Dr Kaufman is an employee of Medtronic. Disclosures for the coauthors are listed in the abstracts.
American Diabetes Association (ADA) 2016 Scientific Sessions; June 14, 2016; New Orleans, Louisiana. Abstracts 77-OR, 79-OR, 99-LB, 378-
www.medscape.com
