Several trials are due to be completed this year, bringing the hope that at least one artificial pancreas system will come to market in 2017.
2016 is an exciting time for the dream of the artificial pancreas. Several much-anticipated trials are due to be completed this year, and they bring the hope that at least one artificial pancreas system will come to market in 2017.
Artificial pancreas systems, otherwise known as closed loop insulin delivery systems, hold the promise of improving nocturnal glycemia and quality of life for people who suffer from type 1 diabetes. Universities, commercial entities, and not-for-profit organizations have all contributed to the effort to develop this new technology. The Food and Drug Administration (FDA) has also supported expedited development of the artificial pancreas by providing guidance about requirements for clinical trial and premarket approval, and a flexible regulatory approach.1 And the National Institutes of Health (NIH) have pledged $20 million to fund advanced safety and efficacy trials.
What Is the Artificial Pancreas?
In a nutshell, an artificial pancreas system consists of three elements: an insulin pump, a system that can sense glucose in real time, and safety and control computer algorithms that can run on an insulin pump, a computer, or a cell phone.1
Insulin-only approaches and dual hormone approaches have both been devised. The dual hormone approach was pioneered by Edward Damiano, PhD (Boston University) and colleagues, and uses insulin plus glucagon. Dual hormone systems that use amylin have also been proposed.
A variety of systems are in development, ranging from fully automated systems that require almost no user input, to hybrid systems that require user input for such things as exercise or meals, and have automated insulin delivery at night.2
The major development in research happened when testing moved out of highly controlled experimental conditions and into the home. The AP@home project, funded by the European Union, consisted of a series of clinical studies run over five years. That project culminated in two studies in which participants used an artificial pancreas system at home for two to three months without physician supervision. Results showed significant improvement in HbA1c, compared to the best currently available therapy.3
Preliminary findings from other studies agree that use of artificial pancreas systems is associated with decreased overall glucose levels, increased time-in-target range, and decreased hypoglycemia, especially at night.4
Development of artificial pancreas systems has met with several challenges. The physiologic delay in insulin action and slow absorption of fast-acting insulin necessitate complex algorithms, and the wide ranges in these variables represents an important hurdle. Algorithms also need to adapt for daytime variables like post-exercise hypoglycemia and meal components like carbohydrates, lipids, and protein. And, changes in insulin sensitivity related to stress, illness, puberty, and menses have not been fully assessed.4 Self-learning algorithms and auxiliary sensors have been proposed to deal with some of these problems.2 Hybrid systems allow for manual insulin boluses at mealtime, and represent an alternative solution.4
Dual hormone systems will likely be more expensive than insulin only systems. Third party payors may require proof of their added advantage in order to agree to reimbursement. In addition, current formulations of glucagon must be reconstituted daily, which limits use.4
Other challenges relate to human factors: user-friendliness, wearability related to device size and weight, visual display, battery life, alarm fatigue, and potential connectivity to the ‘cloud’ for remote-assisted safety monitoring or intervention. Use in pediatric, elderly, and pregnant populations will also need to be explored.5
Several larger trials are in the works. Completion of the first long-term at-home safety trial is expected in May 2016. That trial is testing Medtronic’s hybrid insulin-only MMT-670G closed loop system.2 And, NIH recently funded one of the largest-ever long-term clinical trials of an artificial pancreas system in the home setting. The system uses smart phone technology and was developed at the University of Virginia School of Medicine and Harvard University, and licensed to Type Zero Technologies. The trial has two phases. The first will include 240 patients and compare the device against a control insulin pump. The second constitutes a six-month extension that includes 180 patients from the first phase, and will test the system’s adaptive control algorithm.5
Artificial pancreas systems now in development include: 2
• Animas: Predictive low glucose suspend or hypoglycemia/hyperglycemia minimizer
♦ Potential launch: Unknown
• Bigfoot Biomedical: hybrid, insulin only system, for use 24/7
♦ Potential launch: Late 2018
• Inreda Diabetic: Fully automated closed loop, dual hormone, for use 24/7
♦ Potential launch: Sometime in 2016 (European Union)
• Medtronic: Hybrid, insulin only, for use 24/7
♦ Potential launch: April 2017 (US), April 2018 (Europe)
• Tandem: Predictive low glucose suspend or basal closed loop system
♦ Potential launch: Late 2017
• Boston University: hybrid, dual-hormone, for use 24/7
♦ Potential launch: Approx 2018 (US)
• University of Virginia/Type Zero: hybrid, insulin-only, overnight and 24/7 operation
♦ Intermediate-term studies published to date, clinical trials with up to 6 months are planned for 2016
• University of Cambridge: hybrid, insulin-only, overnight and 24/7 operation
♦ Potential launch: Unknown
So, the race is barreling full steam ahead. With so many systems in development, the future is looking bright for the artificial pancreas, even with the inevitable delays in bringing new products to market. The question is, who will finish first?
• Universities, commercial entities, not-for-profit organizations, the FDA, and the NIH have all supported the development of artificial pancreas systems.
• An artificial pancreas system consists of an insulin pump, a system that can sense glucose in real time, and safety and control computer algorithms.
• Preliminary findings from studies suggest that artificial pancreas systems are associated with decreased overall glucose levels, increased time-in-target range, and decreased hypoglycemia, especially at night.
• At least eight different artificial pancreas systems are in development, of which three could potentially hit the market in the US or Europe within the next year.
1. Food and Drug Administration. The Artificial Pancreas Device System (APDS). Accessed May 20 2016 at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/HomeHealthandConsumer/ConsumerProducts/ArtificialPancreas/default.htm
2. Kropff J, DeVries JH. Continuous glucose monitoring, future products, and update on worldwide artificial pancreas projects. Diabetes Technol Ther. 2016 Feb;18 Suppl 2:S253-263.
3. Heinemann L, et al. AP@home: the artificial pancreas is now at home. J Diabetes Sci Technol. 2016 Feb 16.
4. Ang KH, et al. Combining glucose monitoring and insulin delivery into a single device: current progress and ongoing challenges of the artificial pancreas. Expert Opin Drug Deliv. 2015;12(10):1579-1582.
5. Karoff P. Artificial pancreas system aimed at type 1 diabetes mellitus. Harvard Gazette. http://news.harvard.edu/gazette/story/2016/01/artificial-pancreas-system-aimed-at-type-1-diabetes-mellitus/