For patients with type 1 diabetes mellitus, next-generation insulin pumps will feature sophisticated computer algorithms that automatically calculate and administer precise doses of insulin, or insulin and glucagon, based on data from a continuous glucose monitoring system.
These “closed-loop” or “artificial pancreas” devices would require little or no user input, obviating the need for daily finger pricks. “When available, a fully automated system will reduce the daily burden of self-care” and will help prevent acute and chronic complications of diabetes, said Guillermo Arreaza-Rubín, MD, program director within the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Early trials of artificial pancreas devices are promising, experts say. In one random-order crossover study of adults with type 1 diabetes, a system that automatically administered both insulin and glucagon caused no serious adverse events and achieved significantly better glycemic control than either conventional or glucose sensor-augmented insulin pump therapy, investigators reported in the Jan. 28 Lancet.
Previous trials of artificial pancreas devices have lasted only days or weeks, however. To test the long-term feasibility of these systems, NIDDK has allocated about $41 million to four projects that will begin this year and end in 2020. Outcome measures include safety, efficacy, usability, quality of life, and cost-benefit ratios. A key aim is to help expedite the regulatory approval and commercial availability of these systems, Dr. Arreaza-Rubín said.
These devices will advance diabetes care, but they cannot replace it, the experts emphasized.
“Studies consistently show that interaction between physician and patient leads to success, not the device itself,” said Alan O. Marcus, MD, FACP, of South Orange County Endocrinology in Laguna Hills, Calif. “All these devices are not substitutes for the skill and care of a good internist. Just as important as controlling blood glucose is controlling blood pressure, weight, and cholesterol, and there is no device to do that.”
A hybrid closed-loop system
The most advanced insulin pumps on the U.S. market continuously monitor glucose and automatically suspend insulin delivery when levels drop. They include the Minimed 530G and 630G systems, which are manufactured by Medtronic, said Gregory Forlenza, MD, a pediatric endocrinologist at the Barbara Davis Center for Childhood Diabetes at the University of Colorado Anschutz Medical Campus in Aurora.
These “suspend-on-low” devices have been available in the United States since 2013. But a new device takes things a step further. The Medtronic MiniMed 670G, which was approved by the FDA last year and became available in June, not only “suspends insulin on low” but is the only commercially approved system in the world to automatically deliver basal insulin, said Dr. Forlenza, who has conducted trials sponsored by Medtronic, Insulet, Dexcom, and several other manufacturers of insulin pumps.
Patients can set the 670G pump to one of three levels of automation, according to information provided by Medtronic. The least automated setting suspends insulin delivery for up to two hours when glucose levels reach a preset low threshold. The intermediate setting suspends insulin delivery before levels reach this threshold and resumes giving insulin when levels recover. Finally, the auto mode automatically delivers basal insulin without user input.
However, the 670G is not a truly closed-loop system, Dr. Forlenza emphasized. It is a “hybrid closed-loop system,” because at all three settings, patients must count carbohydrates and must manually bolus insulin at mealtimes. Also, because today's continuous glucose monitoring systems have up to a 15% margin of error, the FDA label for the 670G requires patients to calibrate the sensor by manually checking their blood glucose at least twice a day, he added.
The manual glucose checks are crucial, the experts stressed. “If you have a device that reads [glucose] inaccurately even once and acts on that erroneous information, you can have a deleterious outcome,” Dr. Marcus said.
The 670G has a continuous glucose monitoring sensor, an insulin pump, and an infusion patch that connects to the pump and delivers insulin through a catheter, Dr. Forlenza explained. Its FDA approval was based on a study of 124 outpatients ages 14 to 75 years who had already used another insulin pump for at least six months. During 12 weeks of using the 670G, average HbA1c levels fell from 7.4% to 6.9%. The results were published in the Oct. 4, 2016, JAMA.
A Medtronic spokesperson would not say how many patients preordered the 670G. However, several hundred patients did so at the Barbara Davis Center alone, and insurers have agreed to cover patients there who are ages 14 and older, according to Dr. Forlenza.
Additional “first-generation” artificial pancreas systems will become available in the next two to three years, Dr. Forlenza said. The JDRF (formerly the Juvenile Diabetes Research Foundation) has actively advocated for insurance coverage for these devices, he added. Indeed, these devices will potentially save costs by reducing emergency department and intensive care unit admissions for diabetic hypoglycemia, he said.
Next steps in research
First-generation artificial pancreas devices like the 670G are “the end of the beginning, not the beginning of the end,” Dr. Forlenza said. “We often liken it to cell phones. The first-generation systems will be like 1980s cell phones, not the iPhone 6.”
Thus, in addition to the four academic trials planned by the NIDDK, companies such as Insulet, Tandem, and Bigfoot Biomedical are conducting trials of artificial pancreas systems in inpatient and outpatient settings, Dr. Forlenza said.
Researchers also want to develop smaller, more user-friendly systems that don't require manual insulin bolusing at mealtimes and that incorporate motion sensors, natural language processing, more durable components, and real-time, cloud-based computing, Dr. Forlenza said.
Ease of use is especially important because participants in artificial pancreas studies are highly motivated, and it remains unclear how well these devices will perform for patients who are less engaged in their own care, Dr. Forlenza noted. “Our concern is that patients will hear ‘artificial pancreas' and think that the device will make diabetes care go away,” he said. “We wish that were true, but we're not there yet.”
Dr. Marcus reiterated those comments, noting that up to half of patients stop using medical devices during the months after a trial ends. An artificial pancreas “is not a stent, but something that the patient has to interact with on an ongoing basis, and comfort is a big part of that,” he said.
Very few data are available on artificial pancreas devices in type 2 diabetes, Dr. Forlenza noted. “I suspect that patients with type 2 diabetes who are on insulin therapy will gradually begin to use artificial pancreas systems, but the scientific data is several years behind the data for type 1 patients,” he added. “The systems may also need to be tweaked in terms of how they handle larger insulin doses and more insulin-resistant patients.”
Tips for patient care
Internists can take several steps to help type 1 patients successfully use new artificial pancreas-type devices, the experts said. First, they can correct misassumptions. “For any provider, I think the first major thing is to manage expectations of the technology,” said Dr. Forlenza. “It is not a panacea.”
“There is an idea out there that these pumps are so good that they do everything. That is not true,” agreed Joel Zonszein, MD, FACP, a professor of clinical medicine at the Albert Einstein College of Medicine in New York.
The next step is to reinforce the educational messages patients receive from their endocrinologist, nutritionist, and other members of the diabetes care team, Dr. Zonszein said. Patients need to be educated and reminded to count carbohydrates, bolus prandial insulin, and manually measure blood glucose, he stressed. “I always tell the patients that the device is as good as the person managing it.”
Dr. Forlenza has found that patients do best with an artificial pancreas-type device if they are already testing their blood glucose at least four times per day, counting carbohydrates, and bolusing insulin for all meals and are willing to wear both the sensor and the pump, he said. He also cautioned clinicians to regularly review and fine-tune rates of automated basal insulin delivery, especially in growing children.
Patients also should have their HbA1c levels checked three to four times a year and should see their endocrinologist if the levels creep up, said Dr. Zonszein. Other red flags for referral include recurrent hypoglycemia in the face of insulin therapy, frequent infections, or device failure, Dr. Marcus said.
Finally, and crucially, internists should continue to monitor patients holistically, covering all aspects of metabolic health.
“Controlling blood glucose is only part of the picture,” Dr. Marcus added. “The most important thing is not to silo this patient into diabetes care, just because glucose control is an issue. For example, you don't want the patient just eating what they want because then you will see weight gain and obesity. Blood pressure, cholesterol, diet, and exercise remain huge requirements on the part of the internist and the patient.”