Artificial Pancreas Will Become Reality Within 2 Years

Veronica Hackethal, MD

July 07, 2016

The "artificial pancreas," or nearly closed-loop system, may soon become a reality for patients with type 1 diabetes, with forecasts that a product may come to market as early as this year or certainly by 2018, according to a new review by the UK National Institute for Health Research published online June 30 in Diabetologia.

Authors Hood Thabit, MB BCh, MD, PhD, and Roman Hovorka, MD, of the University of Cambridge, United Kingdom, explain that the artificial pancreas combines continuous glucose monitoring (CGM) with continuous subcutaneous insulin infusion therapy and a control algorithm. A hybrid approach also exists, which allows for bolus administration of insulin after meals.

Closed-loop systems address insulin-requirement variability — average daily variability in insulin is 20% during waking hours and 30% at night, and closed loop systems seem to perform better at night. There are also large variations in insulin requirements between individuals and, even within the same person, insulin requirements can vary by as much as one-third of the normal daily dose up to three times this, depending on factors like exercise, meal composition, and the menstrual cycle.

As such, the artificial pancreas can minimize hyperglycemia and decrease the risk of hypoglycemia related to tight glucose control.

Yet there remain a number of barriers to uptake of the technology, including user adherence and usability, even though people with type 1 diabetes have voiced high interest in the use of such systems and being able to effectively take "time off from the demands of diabetes," say Drs Thabit and Hovorka.

"The artificial pancreas has made great leaps in the past few years, from being tested in small laboratories settings to real life in people's homes. The level of innovation has been very vast," Dr Hovorka told Medscape Medical News.

The progress results from intensive research and generous funding, with at least $200 million poured into the effort by funders over the past decade.

Still, some patients are refusing to wait for commercial devices: a small group of patients in the United States have become so frustrated waiting for the artificial pancreas that they have built their own closed-loop systems, as previously reported by Medscape Medical News.

Trials Successful So Far but Still Some Concerns

Randomized controlled transitional studies in diabetes camps, hotels, and outpatient settings — where participants are studied in "real-world" environments but have close monitoring — support the feasibility and efficacy of closed-loop systems in outpatient settings, as have been variously reported, note Drs Thabit and Hovorka.

And studies in free-living, unsupervised settings in children, adolescents, and adults also show better glucose control/outcomes and in some cases decreased hypoglycemia, as well as favorable user acceptance.

Home studies have also shown improvements in time spent in the target glucose range, without increased hypoglycemia. The longest randomized home study to date has lasted 3 months.

And qualitative studies have supported user acceptance, say the doctors. Issues such as "having time off from their diabetes," less worry and fear about hypoglycemia, and other health-related quality-of-life topics are cited as positives by users.

But there is still concern over the size of devices, device connectivity, and sensor-calibration issues. Also needed are improvements in the control algorithm to control for adaptation and individualization, to improve glucose-sensing inaccuracies and pump-delivery errors. In addition, the issue of cybersecurity and secure communications protocols is of vital importance.

Another challenge is the fact that even fast-acting insulin analogues do not reach their peak levels in the bloodstream until 0.5 to 2 hours after injection, with their effects lasting 3 to 5 hours. This may not be fast enough for effective control in, for example, conditions of vigorous exercise.

Use of the even faster-acting insulin aspart analogue may remove part of this problem, as could use of other forms of insulin such as inhaled insulin, they note.

Baby Steps, but Quick Ones

From here on out, Dr Hovorka expects continued, incremental innovation, although continued investment will be needed to refine these devices, he stressed.

"What is being developed now will be surpassed by new progress," he said.

Nevertheless, "I would expect it to be more likely than not likely that an artificial pancreas will be on the market by 2018. I give it high credentials," he noted.

Regarding the most promising model, Dr Hovorka said, "I don't necessarily support one name or the other. The whole industry is moving forward, although there are some front runners involved."

Components of an artificial pancreas [Source: Diabetologia]

 

One of these is technology from Medtronic, the insulin-only hybrid closed-loop 670G system (MiniMed), slated for approval by the Food and Drug Administration this summer on the basis of pivotal research presented at the recent American Diabetes Association meeting, as reported by Medscape Medical News.

Another prospect is the iLet or "bionic pancreas," a dual hormone system developed by Boston University biomedical engineering professor Edward R Damiano, PhD, and colleagues. The iLet, which is being trialed using both insulin alone in one of the chambers of the device as well as insulin and glucagon together, is being developed by Beta Bionics, a public-benefit corporation.

However, Dr Hovorka believes that "significant challenges" exist for the dual hormone system. Adding glucagon increases the complexity over insulin alone, which has been in use for decades, and necessitates a second pump device. And current glucagon formulations, which require replacement every 24 hours, are unstable, he explains.

Research into dual-chamber pumps and how to formulate more stable glucagon is ongoing: long-term human safety trial data are needed regarding the chronic use of subcutaneous glucagon, for example. And there may be other unknown obstacles, which is not the case for the single hormone.

"Given where we are currently, I think there's no way the dual hormone system will make it for 2018," Dr Hovorka said. "We will start definitely with a single hormone. I'm not against the dual hormone system, I'm just saying that's an area for further research."

Other companies involved in developing closed-loop systems are Animas and Tandem, which is partnering with Dexcom.

Acceptance by Doctors and Widening Patient Base and Reimbursement

In the review, Drs Thabit and Hovorka note that other barriers may come in the form of front-line healthcare professionals themselves: there is a question as to how quickly they will adopt and prescribe any such closed-loop device.

As such, structured education about the use of the device will be key, along with reassuring them that communications remain secure and not vulnerable to cybersecurity threats, unauthorized data retrieval, and interference with wireless protocols.

Another issue will be how to expand the user base to a wider population, including those patients who are not currently using insulin pumps.

"Increasing the user base is really critical for further development," Dr Hovorka commented.

More research is also needed into quality-of-life issues and which populations will benefit most from this new technology.

How will user issues vary among the very young, pregnant women, and those with inpatient hyperglycemia, for example?

And cost-effectiveness data and reimbursement policies will be key.

"The current speculation is that an artificial pancreas should not be more expensive than the combination of sensor and a pump, but the price is to be determined," Dr Hovorka concluded.

The article was supported by the National Institute of Health Research Cambridge Biomedical Research Centre, Efficacy and Mechanism Evaluation National Institute for Health Research, the Leona M & Harry B Helmsley Charitable Trust, JDRF, and the National Institute of Diabetes and Digestive and Kidney Diseases and Diabetes UK. Dr Hovorka reports speaker honoraria from, advisory panel membership on, and licensing fees from and/or consulting for Eli Lilly and Novo Nordisk. He also reports patents and patent applications related to closed-loop systems. Dr Thabit declares no relevant financial relationships.

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Diabetologia. Published online June 30, 2016. Article

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