Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, according to new research.
Automated insulin delivery (AID) system, also known as closed-loop systems or artificial pancreas, connects an insulin pump and a continuous glucose monitor (CGM) to an algorithm that automatically adjusts the administration of insulin to optimize glycemic control.
Before the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner co-developed an algorithm that could link older versions of an insulin pump and CGM.
In 2015 they made the code and all associated materials open-source, so anyone who wanted to build their own AID system could do so. Today, thousands of people with type 1 diabetes around the world use the systems, which are sometimes referred to as “do-it-yourself (DIY)” AID systems, although the approach has been based on the community.
AID systems are not endorsed by any regulatory body, and despite several non-randomized studies demonstrating their effectiveness and safety, some healthcare professionals still have concerns about their safety. In 2019, the United States Food and Drug Administration (FDA) warned against using any unapproved device or algorithm. (Now, however, at least one open-source AID system algorithm is under review by the FDA.)
Aiming to address these concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naïve to AID systems.
Physicians uncomfortable with open source; The study reassures
The findings were presented June 6 at the American Diabetes Association’s 82nd Scientific Session by Martin I. de Bock, PhD, FRACP, pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand .
The study compared the most commonly used open source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparison group.
The open-source AID system led to a significant reduction in A1c without major safety issues.
“Acceptance [among clinicians] open-source systems is diverse and complicated, [with varying] personal comfort level of seeing someone use an AID system that doesn’t have regulatory approval,” de Bock said. Medscape Medical News.
“This is one of the reasons why it was so important to conduct the CREATE trial for the thousands of open source AID users. Since the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – this can help reassure vendors when they see people using an open source automated system,” he said.
Invited to comment, session moderator Diana Isaacs, PharmD, CDCES, clinical endocrine pharmacist at Cleveland Clinic, Ohio, said Medscape Medical News: “There was concern that these systems weren’t safe, so it’s important to show safety. I think people deserve choice. As long as they’re safe, patients should be able to use whatever they want to use, and we should support them.”
Isaacs pointed out that one advantage of open-source systems over current commercial patient aids is the ability to customize glucose targets, but in CREATE those targets were established in the protocol by investigators.
“I think it’s good to have the data, although in the trial they had specific requirements. They had a target range and an active insulin time that they recommended. So it’s a bit different from real DIY where you don’t really have these guidelines that you have to follow. It’s exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
Improved reach time of open-source systems, no security issues
For the CREATE study, 100 participants were recruited, including 50 children aged 7 to 15 and 50 adults aged 16 to 70. All participants had been using insulin pumps for at least 6 months. Most children and about two-thirds of adults also used CGMs, but only 6% of children and 18% of adults had previous experience with AID systems.
Baseline A1c in children was 7.5% and in adults 7.7%.
After a 4-week run-in period, all patients were randomized to receive open source AID or insulin pump plus CGM for 6 months.
The final group analyzed consisted of 42 patients from the open-source AID group and 53 patients from the comparator group.
The primary outcome, the adjusted mean difference in percent time in range (blood glucose 70–180 mg/dL) over the last 2 weeks of the 6-month trial, showed a significant difference of 14% (P
Time in range in the open source AID group increased from 61.2% to 71.2%, while it actually dropped slightly in the comparison group from 57.7% to 54.5% .
The proportion of patients achieving a time in interval >70% with the open source AID was 60% versus only 15% with the pump plus CGM.
Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is very pleasant, since there was concern that the technical load of open source would be [leading to] abandonment, but we did not see it. It was maintained until the end of the trial,” commented de Bock.
Hypoglycemia rates did not differ between the groups and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
No more waiting: what is the future of AID Open Source?
When the open source APS was first developed, users coined the motto: “We don’t wait”. But now that the “wait” is over and several commercial aids have been approved by regulators, with more still in the pipeline, will people still use open source systems?
There is no current data on people switching from DIY to commercial systems. However, de Bock said, “For most who have opted for an open source option, the precision of the settings they can use and enjoy would mean most would probably stick with their open source.”
Isaacs agrees: “Actually, I don’t think it’s going to go away in the near future, because the FDA has very specific criteria for determining where these [formally approved] devices can be in terms of target ranges and requirements compared to open source, you can really customize. So I still think there will be a subset of people who will want that customization, who will want lower targets.”
Dana Lewis, originator of the DIY system and co-author of CREATE, said Medscape Medical News“I don’t believe there’s been a decline, and in fact I think open source AID has continued to be adopted as awareness of the options increases and more pumps and of CGM become interoperable with various AID open source choices.”
“I think the increase in adoption is also influenced by the fact that in places like Europe, Asia and Australia there are warranty pumps on the market that are compatible and interoperable with the “AID open source. I think the global awareness of AID is increasing the adoption of commercial and open source sources,” she said.
“Clinicians, as recent position statements emphasize, must maintain support for the person with diabetes, regardless of the mode of treatment they are undergoing…Health care providers should be encouraged to draw lessons from the experiences of people who have stuck with open-source or dial-up diabetes, so they can learn about the relative strengths and advantages of each system,” de Bock advised.
Lewis noted, “We are seeing a growing awareness and comfort among endocrinologists from the perspective of the community, and we hope this study will help increase conversation and awareness about the safety and effectiveness of systems.” open source AID as an option for people with diabetes.
In fact, the team published an article looking specifically at the clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.
The results of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the 2022 Annual Meeting of the European Association for the Study of diabetes (EASD).
The study was funded by the Health Research Council of New Zealand, with material support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. de Bock said he received honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed and Dexcom. Isaacs said he has been a consultant for LifeScan, Lilly, and Insulet, and a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Lewis has did not report any relevant financial relationships.
ADA Scientific Sessions 2022. Presented June 6, 2022. Abstract 286-OR.
Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She is a regular contributor to Medscape, with other work published in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She’s on Twitter: @MiriamETucker.
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