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Joaquim Cardoso MSc.
The Health Strategist — research, strategy and implementation
September 28, 2022
NEJM
Jennifer Sherr, M.D., Ph.D.
September 29, 2022
Key messages:
- … although population-based studies show that rates of death and cardiovascular disease have decreased over time among persons with type 1 diabetes, a gap exists when comparisons are made with rates in the general population.
- The time is now to close this chasm, and simplified, automated insulin delivery, as with the bionic pancreas, may be the solution.
In January 1922, the management of type 1 diabetes was forever altered when Leonard Thompson became the first person to receive an injection of insulin extract.1
Although treatment with insulin therapy has been possible for more than a century, providers and persons with type 1 diabetes are faced with the grim reality that the attainment of glycemic targets remains elusive for many, increasing the risk of microvascular and macrovascular complications.2
To aid with diabetes management, various technologies have been developed.
Some are aimed at measuring glucose, with continuous glucose monitors that currently offer a plethora of data on which to make treatment decisions, whereas others work to deliver insulin, with insulin pumps that provide more fine-tuned and precise doses than what is feasible with multiple daily injections.
From these foundational components, automated insulin-delivery systems (also known as closed-loop systems) provide a more physiologic approach to diabetes management, tying insulin delivery to sensor glucose values on the basis of algorithms.
Insulin delivery with such devices can be interrupted to avert hypoglycemia, and additional insulin can be autonomously delivered to mitigate hyperglycemia.
A clear picture has emerged regarding the benefits of automated insulin delivery — evident improvements in glycemia, especially overnight.3
Although the ultimate goal for these systems is full automation, given the limitations of subcutaneously delivered rapid-acting insulin analogues, a hybrid approach has been used, whereby the person with diabetes needs to note (i.e., announce) meals, often by entering discrete amounts of carbohydrates about to be consumed.
To date, three such systems have received regulatory approval in the United States, with five systems receiving CE marking.4
In this issue of the Journal, Russell and colleagues5 present the results of a 13-week, multicenter trial in which patients were randomly assigned in a 2:1 ratio to receive either an insulin-only configuration of the bionic pancreas or standard care,
… which could be any method of insulin delivery but necessitated the use of a real-time continuous glucose monitor.
The iLet bionic pancreas (Beta Bionics) differentiates itself from others in that the initiation of automated insulin delivery requires only the entry of a patient’s body weight and its simplified qualitative approach to meal announcements.
The cohort of participants who were enrolled in this trial ranged in age from 6 to 79 years and had baseline glycated hemoglobin levels ranging from 5.5% to 13.1%.
The mode of insulin delivery before enrollment varied among the participants — automated insulin-delivery systems, conventional pumps, and multiple daily injections — and the trial participants were diverse in their racial, ethnic, and educational backgrounds, with more than 15% of the cohort being insured by Medicare, Medicaid, or other government insurance.
During the 13-week trial period, the participants in the bionic-pancreas group had a reduction in the glycated hemoglobin level, from 7.9% to 7.3%, whereas those in the standard-care group had no change in the glycated hemoglobin level (which was 7.7% at both time points).
The time with the glucose level in the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) was 11 percentage points higher with use of the bionic pancreas, a finding that reflects, on average, an increase of more than 2.5 hours per day in the target range.
Although the glycemic outcomes in this trial echo what has been shown with other systems, what makes these findings critically important is that the criteria that are required for use of this mode of insulin delivery actually constitute just one thing: having type 1 diabetes.
With the representation of characteristics that mirror the actual experience of a person with type 1 diabetes, these findings can be more easily generalized to real-world application of the technology when regulatory approval is obtained.
Indeed, one can suppose that with much of the math that plagues diabetes management being alleviated with the bionic pancreas, numeracy skills would not preclude system adoption.
In addition, whereas endocrinologists tend to be concentrated in certain geographic regions in the United States, persons with type 1 diabetes live across the country, which means that many seek care from primary care providers.
Although primary care providers may be eager to offer the best tools, the complexity of the available systems to date has not infrequently impeded prescription.
The feasibility of simplified technologies to overcome this issue is palpable.
Academic societies have altered clinical practice guidelines and standards of medical care to highlight the recommendation that automated insulin delivery should be considered in all persons with diabetes who can safely use available technology.6–8
Now, the goal will be to ensure that access to such technologies is not limited because of insurance coverage or perceptions about who may be an “ideal” candidate for such treatment.
Recent registry data have highlighted the finding that the provision of subsidized continuous glucose monitors has led to an exponential growth in sensor use, with a concomitant reduction in glycated hemoglobin levels that were maintained over a 2-year period.9
These results are impressive, but there is no doubt that automated insulin delivery will be even more promising in the outcomes that it will achieve.
In fact, although population-based studies show that rates of death and cardiovascular disease have decreased over time among persons with type 1 diabetes, a gap exists when comparisons are made with rates in the general population.10
The time is now to close this chasm, and simplified, automated insulin delivery, as with the bionic pancreas, may be the solution.
… although population-based studies show that rates of death and cardiovascular disease have decreased over time among persons with type 1 diabetes, a gap exists when comparisons are made with rates in the general population.10
The time is now to close this chasm, and simplified, automated insulin delivery, as with the bionic pancreas, may be the solution.
Author Affiliations
Jennifer Sherr, M.D., Ph.D.
From the Department of Pediatrics,
Yale School of Medicine, New Haven, CT.
Originally published at https://www.nejm.org.
Related articles
National Institutes of Health (NIH)
Wednesday, September 28, 2022
Bionic pancreas improves type 1 diabetes management compared to standard insulin delivery methods [excerpt]
Next-generation technology maintains blood glucose levels by automatically delivering insulin.
A device known as a bionic pancreas, which uses next-generation technology to automatically deliver insulin, was more effective at maintaining blood glucose (sugar) levels within normal range than standard-of-care management among people with type 1 diabetes, a new multicenter clinical trial has found. The trial was primarily funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, and published in the New England Journal of Medicine(link is external).
Automated insulin delivery systems, also called artificial pancreas or closed-loop control systems, track a person’s blood glucose levels using a continuous glucose monitor and automatically deliver the hormone insulin when needed using an insulin pump. These systems replace reliance on testing glucose level by fingerstick, continuous glucose monitor with separate insulin delivery through multiple daily injections, or a pump without automation.
Compared to other available artificial pancreas technologies, the bionic pancreas requires less user input and provides more automation because the device’s algorithms continually adjust insulin doses automatically based on users’ needs. Users initialize the bionic pancreas by entering their body weight into the device’s dosing software at the time of first use.
Users of the bionic pancreas also do not have to count carbohydrates, nor initiate doses of insulin to correct for high blood glucose. In addition, health care providers do not need to make periodic adjustments to the settings of the device.
“Keeping tight control over blood glucose is important in managing diabetes and is the best way to prevent complications like eye, nerve, kidney, and cardiovascular disease down the road,” said Dr. Guillermo Arreaza-Rubín, director of NIDDK’s diabetes technology program. “The bionic pancreas technology introduces a new level of ease to the day-to-day management of type 1 diabetes, which may contribute to improved quality of life.”
The 13-week trial, conducted at 16 clinical sites across the United States, enrolled 326 participants ages 6 to 79 years who had type 1 diabetes and had been using insulin for at least one year. Participants were randomly assigned to either a treatment group using the bionic pancreas device or a standard-of-care control group using their personal pre-study insulin delivery method. All participants in the control group were provided with a continuous glucose monitor, and nearly one-third of the control group were using commercially available artificial pancreas technology during the study.
In participants using the bionic pancreas, glycated hemoglobin, a measure of a person’s long-term blood glucose control, improved from 7.9% to 7.3%, yet remained unchanged among the standard-of-care control group. The bionic pancreas group participants spent 11% more time, approximately 2.5 hours per day, within the targeted blood glucose range compared to the control group. These results were similar in youth and adult participants, and improvements in blood glucose control were greatest among participants who had higher blood glucose levels at the beginning of the study.
“Our observation that this system can safely improve glucose control to the degree we found, and do so despite requiring much less input from users and their health care providers, has important implications for children and adults living with diabetes,” said Dr. Steven Russell, study chair, associate professor of medicine at Harvard Medical School, and staff physician at the Massachusetts General Hospital in Boston.
Hyperglycemia, or high blood glucose, caused by problems with insulin pump equipment, was the most frequently reported adverse event in the bionic pancreas group. The number of mild hypoglycemia events, or low blood glucose, was low and was not different between the groups. The frequency of severe hypoglycemia was not statistically different between the standard of care and bionic pancreas groups.
Four companion papers were also published in Diabetes Technology and Therapeutics, two of which provided more detailed results among the adult and youth participants. The third paper reported results from an extension study in which the participants from the standard-of-care control group switched to using the bionic pancreas for 13 weeks and experienced improvements in glucose control similar to the bionic pancreas group in the randomized trial. In the fourth paper, results showed that using the bionic pancreas with a faster-acting insulin in 114 adult participants improved glucose control as effectively as using the device with standard insulin.
“NIDDK’s decades-long investment in developing advanced technologies for diabetes management has reached another promising milestone and continues to provide significant return,” said NIDDK Director Dr. Griffin P. Rodgers. “While we continue to search for a cure for type 1 diabetes, devices like the bionic pancreas can allow people to worry less about their blood-glucose levels and focus more on living their fullest, healthiest lives.”
Dr. Edward Damiano, project principal investigator, professor of biomedical engineering at Boston University, and founder and executive chair of Beta Bionics, Inc., concurs. “The completion of this study represents a major milestone for the bionic pancreas initiative, which simply would not have been possible had it not been for the support provided by the NIDDK over the years.”
The study is one of several pivotal trials funded by NIDDK to advance artificial pancreas technology and look at factors including safety, efficacy, user-friendliness, physical and emotional health of participants, and cost. To date, these trials have provided the important safety and efficacy data needed for regulatory review and licensure to make the technology commercially available. The Jaeb Center for Health Research in Tampa, Florida, served as coordinating center.
Funding for the study was provided by NIDDK grant 1UC4DK108612 to Boston University, by an Investigator-Initiated Study award from Novo Nordisk, and by Beta Bionics, Inc., which also provided the experimental bionic pancreas devices used in the study.
Insulin and some supplies were donated by Novo Nordisk, Eli Lilly, Dexcom, and Ascensia Diabetes Care. Partial support for the development of the experimental bionic pancreas device was provided by NIDDK Small Business Innovation Research (SBIR) grant 1R44DK120234 to Beta Bionics, Inc.
The NIDDK, a component of the NIH, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans. For more information about the NIDDK and its programs, see https://www.niddk.nih.gov/.
Originally published at:
Dr. Edward Damiano, project principal investigator, professor of biomedical engineering at Boston University, and founder and executive chair of Beta Bionics, Inc.,
