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In new era of diabetes tech, advancements poised to change management for type 1 and type 2
Diabetes technology has long been offered as an answer to the need for disease management for growing numbers of patients. Particularly for those with type 1 diabetes, insulin pumps, continuous glucose monitors and other “smart” devices, it is hoped, can help to better regulate blood glucose and reduce disease complications, all while simplifying management of a complicated disease. Yet overall uptake of such devices has remained low due to a combination of barriers, including cost, patient access, and large or bulky technology that was not the most user-friendly.
That trend may be changing.
In the past 2 years, the FDA approved several new developments in diabetes technology, including a factory-calibrated, finger-stick-free CGM (FreeStyle Libre Flash, Abbott), a new stand-alone, smartphone-only CGM (Guardian Connect, Medtronic), a “smart” insulin pen that keeps track of dosing (InPen, Companion Medical) and the first artificial pancreas (MiniMed 670G, Medtronic). The pace of new approvals, according to experts, may signal a new era in diabetes technology.
“This is an exciting time for people with diabetes because the whole concept of technology is to give people the tools that they can use to improve outcomes,” Martin J. Abrahamson, MB, ChB, associate professor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, told Endocrine Today. “I think we’re beginning to see that happening.”
The biggest technology advances, Abrahamson said, tend to fall into three main areas: smaller, more accurate CGM; simpler, more user-friendly insulin pumps; and the enhanced connectivity of new digital health components, such as diabetes apps, algorithms and cloud technology.
“In the past 5 years, we’ve seen an incredible acceleration in the capacity to perform glucose sensing in a more effective and accurate way,” Anne L. Peters, MD, professor of clinical medicine at Keck School of Medicine at the University of Southern California, Los Angeles, told Endocrine Today. “Because we can do that, we can then do things like closed-loop systems, where we have more accurate insulin dosing. The other technologies, in terms of the more wired, internet-based systems, seem to me to be just on the threshold of evolving because the FDA is finally approving ‘bolus wizards’ and things that allow us to help patients who aren’t on pumps dose properly.”
Still more cutting-edge developments are in the research pipeline, including a “tubeless” artificial pancreas (Omnipod Horizon, Insulet), a “mini” CGM with an extended-wear, disposable sensor (a partnership between Dexcom and Google’s Verily Life Sciences), and a 90-day, implantable glucose sensor (Eversense, Senseonics), currently awaiting FDA approval.
Additionally, after heavy lobbying from diabetes stakeholders, CMS in early 2017 determined that CGM devices approved for use in treatment decisions are eligible for Medicare coverage, opening the door for more patient access.
“The broader availability of CGM, the improved accuracy of CGM and, therefore, its greater usefulness has led to the ability to start having novel uses for CGM, like driving automated insulin delivery, the first on the market being the Medtronic 670G,” Robert A. Gabbay, MD, PhD, FACP, chief medical officer and senior vice president at Joslin Diabetes Center in Boston, told Endocrine Today. “In the history of diabetes, there was urine testing, and then it went to finger sticks, and that’s where it’s been for years and years. Now, there are viable and effective alternatives. Those are big milestones.”
Advancements in sensors, CGM
The latest sensor and CGM developments, coupled with expanded Medicare coverage, have put devices initially designed for people with type 1 diabetes into the reach of those with type 2, setting the stage for better management and, ideally, better outcomes on a much larger scale, according to experts.
“While initially we thought CGM might be great for people with type 1 diabetes, we’re seeing it in more people with type 2 and not necessarily confined to people who take insulin,” Abrahamson said. “It has further use in people who are relatively recently diagnosed because, even if you use it temporarily, it can give you a snapshot of what’s really going on in your world, so to speak.”
Richard M. Bergenstal, MD, executive director of the International Diabetes Center Park Nicollet in Minneapolis, agreed.
“CGM has come along, and the other important thing is it’s for all-comers,” Bergenstal, a former president of the American Diabetes Association, told Endocrine Today. “We used to think of it as the next step after a pump. Now, many studies have shown the value of it with [multiple daily injection] patients as well. CGM is now rapidly becoming the first technology patients reach for after [multiple daily injection]. That’s been a big change just in the past couple of years.”
This follows two big CGM approvals in the past 10 months: the Freestyle Libre Flash Glucose Monitoring System, approved by the FDA in September, and the Dexcom G6 integrated CGM system, approved in March. Both systems are factory calibrated and do not require confirmatory finger-stick testing, eliminating a hurdle for many patients.
The G6, according to Dexcom, will also be the first device approved for use as part of an integrated system with compatible devices and electronic interfaces, including dosing systems, insulin pumps, blood glucose meters or other diabetes management electronic devices. The approval also grants the device de novo classification, putting it in a category called special controls, which enables future integrated CGM system developers to bring their products to market. The FDA is currently developing criteria for future special controls outlining requirements for ensuring integrated CGM accuracy, reliability and clinical relevance.
“The calibration piece, where that becomes an advantage is that it starts to open up the number of people that can make use of these devices,” Gabbay said. “CGM has largely been a type 1 tool, but there are many people with type 2 that could benefit from this.”
More novel sensor technology may be available soon. In March, an FDA advisory panel unanimously recommended approval of the Eversense CGM, a fluorescence-based system that is implanted in the upper arm in a 5- to 10-minute office-based procedure. The implanted sensor lasts 90 days, after which it is removed with another short procedure and replaced. An external transmitter is taped on the skin above the implant to allow the glucose monitor to work with its accompanying smartphone or tablet mobile app. The FDA advisory panel’s recommendations are nonbinding, although the FDA often follows its suggestions.
Satish K. Garg, MD, professor of medicine and pediatrics at the Barbara Davis Center for Diabetes at the University of Colorado Denver, said the latest advances will soon be incorporated into standard care for any patient with diabetes.
“I would say, if not within 5 years, definitely in the next 10 years, sensors will take over for the glucose meters, and meters will be a thing of the past,” Garg, also editor of Diabetes Technology & Therapeutics, told Endocrine Today. “What is coming in the pipeline — like with Google’s Verily, which we will start evaluating later this year, and the new Abbott Freestyle Libre, and the new Medtronic sensor, all wearable for 10 to 15 days with little or no calibration needed — that is where the future is going, with CGM. These advances have changed the whole field. That’s one of the reasons that Johnson & Johnson and Roche walked away from the [blood glucose] meter. The field is changing.
“I still remember when I published the first study 20 years ago on GlucoWatch and iPro and all these sensors, and people laughed and said, ‘Who is going to use these?’” Garg said. “Here we are, 20 years later, the whole field is changing to using only sensors. I don’t even look at meter downloads [in clinic]. I only look at sensor downloads.”
Promise of closed-loop systems
In September 2016, the FDA approved Medtronic’s MiniMed 670G, often referred to as an artificial pancreas, to monitor glucose and provide appropriate insulin doses for people aged 14 years and older with type 1 diabetes. This first hybrid closed-loop system includes the Medtronic MiniMed 670G pump, the Guardian Sensor 3 and SmartGuard algorithm, which increases time-in-range with automatic basal insulin delivery based on real-time data. The approval came after pivotal data were presented at the American Diabetes Association Scientific Sessions in New Orleans in June 2016, which showed improvements over baseline in all areas: HbA1c, time in optimal blood glucose range, and hyperglycemic and hypoglycemic events.
In February, the FDA approved a new indication for the Guardian Sensor 3, allowing the device to be worn on the upper arm, likely improving accuracy with the 670G system.
“One big advantage of this system is it literally eliminates nocturnal hypoglycemia,” Garg said. But for all of its advantages, the 670G has some drawbacks, experts note, in part due to its “hybrid” nature. As a condition of approval, the FDA requires that the closed-loop target be set at 120 mg/dL, with the ability to periodically raise the target to 150 mg/dL to allow for increased physical activity, Peters said.
“The problem with having it at a fixed 120 mg/dL is it settles everyone’s HbA1c at about 6.8%,” Peters said. “And it’s great at doing that. But, I’ve had patients whose HbA1c going into this is 6.1% or 6.2%, and they fight this system all the time because the system is trying to bring them to its target.”
Additionally, Garg said, some patients struggle with their role of delivering a correct, premeal bolus at the appropriate time to achieve postprandial glucose control, which requires an accurate carbohydrate count.
“The real issue is most people don’t count carbs, and with this system, you must count some degree of carbs or else you can’t take the bolus,” Garg said. “That’s why it’s a hybrid closed loop. Patients under-bolus it and then, even after 3 months, they haven’t gotten a handle on it because the boluses need to be better aligned.”
More advances in closed-loop technology are on the horizon. In January, Tandem Diabetes Care, maker of the only touchscreen insulin pumps available in the United States, reported the successful completion of the first pilot study using a hybrid closed-loop system featuring its t:slim X2 insulin pump with embedded algorithms from TypeZero Technologies, and integration with Dexcom G6 CGM. This pilot study was the first of three in the NIH-funded International Diabetes Closed Loop (IDCL) trial using the t:slim X2 insulin pump running the algorithm directly on the pump.
The IDCL trial is expected to conclude with a pivotal study in 2018, and Tandem plans to use these data in a premarket approval submission to the FDA, the company stated in a press release.
In December, Bigfoot Biomedical announced it raised $37 million to move its automated insulin infusion device, Bigfoot Loop, into a pivotal clinical trial in the U.S. in 2018. The company is also developing Bigfoot Inject, an auto-titrating connected insulin pen-based system.
In February, Insulet announced new data for its Omnipod Horizon automated hybrid closed-loop system, which was presented at the 11th International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) congress in Vienna. Two studies demonstrated that the Omnipod Horizon algorithm performed well in response to meal challenges and exercise in 24 adults with type 1 diabetes. Results showed strong blood glucose control with time-in-range of approximately 75% and 85% with real-life challenges, including high-fat meals and moderate-intensity exercise.
Beta Bionics is currently working on a dual-hormone system, which would regulate both highs and lows with insulin and glucagon. It has entered into a partnership with Zealand Pharma, a peptide drug development company based in Denmark, to develop this system. Animas’ Vibe pump with Dexcom G4 Platinum CGM has been FDA approved in children and adults, but it is unclear when the company will take this system to clinical trials as a closed-loop or hybrid closed-loop system.
“Any advances will be more versions of what is, at least initially, similar products,” Gabbay said. “The next breakthrough is being able to deal with mealtime glucose levels and exercise. Those are the two places where the automated insulin delivery approach is not so effective. The initial work by them and Insulet is unlikely to tackle that piece, but it will provide alternatives to 670G.
“What’s the advantage?” Gabbay said. “It’s the advantage of the t:slim pump being smaller or the Omnipod system being wireless. It gives people more choice, and that is always helpful.”
Access is key
Multiple hurdles still stand between the typical person with diabetes and technology that could potentially improve disease management and outcomes. In an analysis conducted by T1D Exchange, researchers assessed factors associated with device discontinuation from 2,452 adults with type 1 diabetes enrolled in the T1D Exchange Clinic Registry for at least 1 year. Those who discontinued pump therapy within 1 year reported several reasons, including problems with insertion/adhesive (60%), using a pump was too expensive or not covered by insurance (45%) or the pump was uncomfortable to wear (39%). Among those who discontinued CGM use within 1 year, 71% reported that they felt the device was not accurate enough or not working properly, whereas 33% reported already using an insulin pump and not wanting devices on two sites on the body.
“Here at the Barbara Davis Center, we have about 800 patients on the hybrid closed-loop system out of 7,000, and I don’t think we’ll even get close to 1,000,” Garg said. “Even in a center like ours, that’s the max. In the overall population, it would be greedy to expect more than 5% to 10% of people going on some sort of a hybrid closed-loop system.”
For most of the millions of people living with diabetes, the future lies in the individual pieces that make up something like artificial pancreas technology, Garg said.
“As much as I love the Medtronic 670G ... this is not the answer for most patients requiring insulin therapy,” Garg said. “The answer will be some sort of CGM, some sort of smart pen, like InPen, or one with a memory device, and all the data fed to a software package in an app, which can advise the patients on how much insulin to take. That’s where the future needs to be.”
In the meantime, Peters said, she wants to work toward a goal of “sensors for all.”
“I use them in people with prediabetes, and people with diabetes on pills, and people with diabetes on anything, not continuously, but episodically,” Peters said. “I believe that a sensor should be like a Fitbit, that you can just get over the counter — like you can in Europe — and you can just look at your blood sugars. It’s striking how high people go postprandially after they eat carbs. I use it to figure out where people are. It’s so helpful to me.”
Universal device downloaders and standardized data reports are another needed development, Bergenstal said, to eliminate the need for multiple device readers in a clinic and information presented in multiple, often confusing ways.
“Clinics want options, they want choices,” Bergenstal said. “Do they really have to have six different stations to download data? Part of [the solution] is to have great technology and good studies. But you can have the best diabetes data and not have it fitted to your workflow, and then things don’t get prescribed or downloaded.”
The technology works, Peters said, but people with diabetes must be able to understand it and afford it.
“I spend half my time in east LA, where most people don’t have access to this technology and can’t even use insulin pens,” Peters said. “You can’t forget that the majority of people with type 1 diabetes aren’t higher socioeconomic status, access-to-all-the-stuff people. They’re people in primary care practices all over the country. Not everyone has a smartphone. Not everyone is numeric. Not everyone can do this stuff. No matter what, the goal is to make these advances available to everybody.” – by Regina Schaffer
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- References:
- CDC. National Diabetes Statistics Report. Available at: www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed April 30, 2018.
- T1D Exchange. Why do some people with T1D stop using a pump or CGM? Available at: t1dexchange.org/pages/why-do-some-people-with-t1d-stop-using-a-pump-and-cgm/. Accessed April 30, 2018.
- For more information:
- Martin J. Abrahamson, MD, ChB, can be reached at Beth Israel Deaconess Medical Center, Division of Endocrine GZ-811, 330 Brookline Ave., Boston, MA 02215; email: mabraham@bidmc.harvard.edu.
- Richard M. Bergenstal, MD, can be reached at the International Diabetes Center, 3800 Park Nicollet Blvd., Minneapolis, MN 55416; email: richard.bergenstal@parknicollet.com.
- Robert A. Gabbay, MD, PhD, FACP, can be reached at Joslin Diabetes Center, One Joslin Place, Boston, MA 02215; email: robert.gabbay@joslin.harvard.edu.
- Satish K. Garg, MD, can be reached at the Barbara Davis Center for Diabetes, University of Colorado Denver, 1775 Aurora Court, Room M20-1323, Aurora, CO 80045; email: satish.garg@ucdenver.edu.
- Anne L. Peters, MD, can be reached at the USC Clinical Diabetes Program, 150 N. Robertson Blvd., Suite #210, Beverly Hills, CA 90211-2142; email: annepete@med.usc.edu.
- Disclosures: Abrahamson reports he has served on advisory boards for Novo Nordisk. Bergenstal reports he has received grants and his institution has contracted for on consulting/advisory board services for Novo Nordisk, Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Bristol-Myers Squibb/AstraZeneca, Calibra, Eli Lilly, Hygieia, Johnson & Johnson, Medtronic, Roche, Sanofi, Takeda and Dexcom. Gabbay reports he has consulted for HealthReveal and Onduo. Garg reports he has served on advisory boards for Dexcom, Eli Lilly, Lexicon, MannKind Corp., Medtronic, Merck, Roche and Sanofi, and has received research grants through his institution from Animas, Dario, Dexcom, Eli Lilly, JDRF, Lexicon, Medtronic, Merck, National Cancer Institute, NIDDK, Novo Nordisk, Sanofi and T1D Exchange. Peters reports various financial ties with Abbott, Becton Dickinson, Bigfoot, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Lexicon, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, Sanofi and Science 37.