Conference Coverage: ADA, AADE

ADA 2017Experts Offer Perspectives on “What’s Now and What’s Next” for Artificial Pancreas Systems

At a symposium during the 77th Scientific Sessions of the American Diabetes Association, researchers discussed the progress that has been made in developing hybrid closed-loop (HCL) insulin delivery systems—and what challenges remain.Also known as an “artificial pancreas,” an HCL system consists of an insulin pump and sensor that uses an algorithm to continuously monitor glucose and adjust insulin dosing. These systems aim to reduce glycemic variability and make it easier for patients with diabetes to stay in their target glucose range.¹

Roman Hovorka, PhD, of the University of Cambridge, kicked off the symposium by presenting the perspective from Europe, where recent study results demonstrate promising outcomes with HCL systems in outpatients with diabetes. The technology is such a hot topic that a question about the artificial pancreas appeared on the General Certificate of Secondary Education exams taken by 16-year-old students in the United Kingdom.

Hovorka highlighted the promising results of several European trials that saw patients with diabetes improve their time in target glucose range and lower their rate of hypoglycemic events when using HCL systems. For instance, the Pediatric Artificial Pancreas project tested such a device in children with type 1 diabetes (T1D) attending an overnight camp in Italy and found that their time in hypoglycemia was 3-fold lower than when they used a standard insulin pump.²

Another study he discussed tested HCL insulin systems in pregnant women with T1D in the United Kingdom and found that the systems improved the time in target glucose range and reduced incidences of hyperglycemia compared with standard pump therapy, both overnight and over a 24-hour period.³ Even when the women went into labor, there were no instances of hypoglycemia during the 24 hours before and 48 hours after delivery. Notably, the women reported improved sleep, reduced worry, and feelings of empowerment and reassurance while using the HCL system to control their glucose levels.

When taken together, Hovorka said, these study findings provide evidence that HCL systems can increase time in optimal glucose range and are well tolerated by users and in pediatric populations and their guardians.

Eda Cengiz, MD, MHS, FAAP, associate professor of pediatrics at Yale School of Medicine, offered her take on “what’s now and what’s next” in HCL systems from the American perspective. She highlighted the evident need for better glucose management, as a majority of patients with diabetes have poorly controlled glycated hemoglobin levels and the dangers of complications are ever-present.

After providing an overview of the terminology associated with continuous glucose monitoring systems, including HCL systems, Cengiz discussed the findings of a study on Medtronic’s MiniMed 670G, the first HCL system to enter the US market.⁴ This insulin-only system increased time in target glucose range for adults and adolescents with T1D by reducing hyperglycemia and hypoglycemia and was shown to reduce glycemic variability.

The study, which was conducted while patients were at home and did not require meal restrictions, found that the MiniMed 670G was well tolerated and that patients reported high satisfaction and quality of life while using the device. No events of diabetic ketoacidosis or severe hypoglycemia were observed in either the adults or adolescents.

Cengiz also described several studies that tested the HCL systems with exercise or other challenging conditions. For instance, the Type Zero DiAs system was tested while users were skiing and among typical adolescents who may forget to deliver an insulin bolus; results showed that it reduced time in hypoglycemia and resulted in better glycemic metric outcomes.⁵ Researchers observed some alarm burnout, but 100% of participants described the system as beneficial.

With these successful findings in mind, Cengiz acknowledged some opportunities for artificial pancreas systems to improve. She said they need to be tested in broader, more representative patient populations and noted that after-meal glucose control could be better achieved through the use of ultra—fast acting insulins. Finally, the burden to the patient needs to be alleviated by creating more user-friendly systems and providing more device training and support. HCL systems, Cengiz said, represent a new, team-based approach to diabetes management that requires patients and providers to think of technology as an ally.

“There is a digital revolution going on everywhere in our lives, and it’s unrealistic to think that diabetes will be isolated from this technology revolution,” she concluded.

--Christina Mattina

CGM “Debate” Finds Benefits, Barriers to Uptake in Type 2 Diabetes

The mood was light—where else do presenters’ slides feature the back side of a rhinoceros and a smiling monkey—but the message was serious: after decades of trying and more than 40 drugs with FDA approval, large numbers of patients with type 2 diabetes (T2D) still have poor glycemic control.

Could broader use of continuous glucose monitoring (CGM) be the answer in T2D? For the right patients, yes, but the challenge is identifying those patients, according to Jeremy Pettus, MD, and William H. Polonsky, PhD, CDE, both from the University of California at San Diego, the host city for the 77th Scientific Sessions of the American Diabetes Association (ADA), which took place June 9-13, 2017.

The ADA session, Should Continuous Glucose Monitoring Be Prescribed for People with Type 2 Diabetes? A Pro/Con Discussion, was styled as a debate, but Pettus and Polonsky turned it into a lively exchange of evidence that supports CGM for patients with T2D, along with research gaps and practical barriers to bringing the technology to more patients.

They started with a key ground rule: they had refused to debate CGM use for patients with type 1 diabetes (T1D) because it’s the standard of care, but they took note of the recent Medicare rule change that would soon bring Dexcom’s G5 to beneficiaries on intensive insulin therapy, which affects most patients with T1D and some with T2D.¹

After Polonsky took the “con” position for sections on patients who use insulin, he and Pettus switched sides—and suit jackets—to debate CGM use for those with T2D using oral medication, who represent most patients with diabetes. Pettus started with an update from the DIAMOND study, which had previously shown that CGM was just as effective for patients with T1D using multiple daily injections of insulin as those using pump therapy.² New data from patients with T1D and T2D who use CGM show that it helps those using daily injections across both patient groups.³

The question about CGM, Pettus posed, is, is it worth the burden and the cost? It’s worth noting, he said, that patients associate how sick they are with the number of medications they take. Unlike medication, CGM has “no side effects.”

There are concerns about patients learning to use CGM, especially if they develop T2D when they are older and less tech savvy. Pettus said there’s other evidence that shows that with limited instruction, a 1-page handout, patients with T2D learned to use CGM and it made a difference.

What’s more, he said, it made the biggest difference in patients with glycated hemoglobin above 9%, a group that “we might write off as hopeless.”For these patients, seeing what certain foods and exercise does to blood sugar proves an eye-opener. “People seeing it in real time is empowering,” Pettus said.

Many assume CGM will require more of a doctor’s time, but it could require less in the long run. “We have a paternalistic view of medicine, and that’s just not the case with CGM,” Pettus said. Armed with better tools, patients “might not need us, and that’s OK.”

Polonsky said the main challenge is that patients with T2D with the most severe hypoglycemia haven’t been studied—and they should be. He read from one of Pettus’ papers to raise the question whether patients had the confidence to actually use their CGM consistently. “Maybe,” Polonsky said, “but we need more evidence.”

Pettus sought to dispel several myths about CGM and basal insulin: (1) titration with self-monitoring isn’t perfect; (2) people will use the results, as seen in one study that showed patients using CGM ate fewer calories, lost weight, and exercised more; (3) hypoglycemia is a significant problem in T2D, and tests with CGM showed people had events that might have gone unnoticed, but the CGM allowed them to act.

In response, Polonsky said a 2014 study involving CGM in patients with T2D on basal insulin produced great results—but also involved frequent contact with the patients. There were 10 visits over 6 months, more than would happen in the real world.⁴ “Was it the CGM or the remarkable support these folks got?” he asked.

When Pettus and Polonsky switched sides to discuss CGM use for those on oral agents, Polonsky—who is an advocate of advancing CGM in the right populations—presented data to show the dismal picture of T2D, despite the ever-increasing number of medication choices. “Why is it that so many folks have a tough time taking medications?” he asked. “Nobody is unmotivated to want to live a long life. We are, at best, ambivalent.”

“We know there are active fears about medication,” he added. By contrast, CGM can offer a chance “to become engaged and stay engaged.”

The use of feedback, he said, “is the most underutilized tool we have.”

For some patients, CGM doesn’t have to be all the time or forever. Polonsky envisions that some patients with T2D could “rent” a CGM device for a month, then maybe a few weeks a year, to get in touch with the patterns of their behavior and the effect on glycemic control. Polonsky knows there’s an argument that patients will never understand the data. That’s the

wrong way to think, he said. “What if we provided help and support so they know what these numbers mean? Can we help people have this ‘Aha!’ experience?” he asked.

He read a case study of a patient with T2D who started using CGM and now couldn’t imagine going back to “being blind” managing his diabetes without it. “The government might not think I need this,” the person wrote, referencing Medicare’s old policy, “but you’ll have to pry it from my cold, dead hands.”

Pettus ended with a photo of a crowded waiting room, likely in a primary physician’s office. The practical reality, he said, is that time constraints and insurance barriers make it too easy to just write a prescription than to take time to teach patients how to use CGM. Pettus and Polonsky agree that CGM should only be tried in patients who show some willingness. The question is how to identify who they are, and they agreed more evidence is needed. CGM costs would need to come down, and the technology would have to become even easier to use. Insurance coverage will remain a barrier until there’s more evidence that the technology is cost-effective.

Polonsky said the idea that patients with T2D might not use CGM because doctors are too busy, “makes me very sad.”

--Mary Caffrey

AADE 2017

For Diabetes Educators, Technology at Every Turn

From the enthusiastic crowd at the keynote address, “Let’s Get Digital,” to an exhibit floor where device makers consumed more real estate than drug companies, there was no missing technology’s rise in diabetes management. And there’s more to come, along with policy questions, said speakers at the annual meeting of the American Association of Diabetes Educators (AADE), held August 4-7, 2017, in Indianapolis, Indiana.

Digital health attracted $450 million in venture capital and continuous glucose monitoring (CGM) grabbed another $250 million in 2016, according to Christopher J. Bergstrom, MBA, an associate director at Boston Consulting Group, who spoke on August 6. Technology’s role in both treating and preventing diabetes is crucial, notwithstanding CMS’ early decision to leave digital providers out of the 2018 launch of the Medicare Diabetes Prevention Program.¹

“There’s one thing I know,” Bergstrom said. “Digital will be part of it. Why? There [are] 84 million people with prediabetes!”²

He noted the alliances that have formed between startups and medical device mainstays, and between tech giants, like Google’s Verily and pharmaceutical giant Sanofi. The marriage of healthcare and data will bear dividends that have yet to be fully understood. “The new data sets are the patient-centered data sets,” he said.

What can insurance companies learn about diabetes and depression from scanning 30,000 social media posts? Companies like Medtronic are asking, “How do we go beyond the pill?”

Role of Diabetes Educators

Diabetes educators are the foot soldiers who teach patients to use blood glucose meters, CGM systems, and digital tools that let patients track their personal data or share it with providers. The era of population health—and accountability for patients’ glycemic control—made for a standing room-only crowd at Abbott’s presentation on the FreeStyle Libre Pro, which lets an educator or physician collect 2 weeks’ worth of data with no effort from the patient. FreeStyle Libre Pro won FDA approval 1 month after last year’s AADE meeting, just one of many technology developments over the past year.³

Also at the meeting, many educators wanted details on how to bill Medicare for Dexcom’s G5 continuous glucose monitor—and why CMS won’t let patients use their smartphone.⁴ And on August 7, MannKind Corp, maker of inhaled insulin Afrezza, announced at the meeting it would be part of a clinical trial with One Drop, the digital device platform, evaluating its effectiveness in combination with the management tool.⁵ Not every digital health tool can serve every purpose, but various ones on the market can:

• Track patient data, which clinicians can use to make medication adjustments • Offer reminders to take medication • Offers AADE’s curriculum through a smartphone,⁶ such as what WellDoc’s BlueStar system can do. • Provide real-time feedback for patients managing their disease.

Digital Health and the Triple Aim

On Sunday afternoon, Kevin Clauson, PharmD, associate professor of Lipscomb University, addressed how diabetes educators can harness the potential of digital health. As digital tools become smaller, less expensive, and better connected to health systems, they have the potential to improve self-care, deliver a better patient experience, and lower costs. The catch, he said, is that patient data will become a commodity.

Clauson said educators must be mindful of this when their patients have opportunities to use free or low-cost options. He reviewed more up-and-coming technological tools, many of which could improve medication adherence. Proteus Digital Health, which received attention throughout the meeting, can include a digestible sensor in a pill, which offers the first fool-proof way of measuring adherence. Type 2 diabetes and hypertension are high on its list of target conditions.⁷ Apple, he said, also is working on another step: “middleware” will let health systems connect all of the data from thousands of apps and wearables into usable information that can be integrated into an electronic health record.

However, the questions here are not just technical. Health systems are concerned about being overwhelmed with patient data and being held liable if they fail to act on something that lands in patient record.

As Bergstrom said in his morning talk, the ethical and policy questions will come faster than anyone realizes. The next generation of tools is at the doorstep. “There’s going to be a tipping point, right before we know it,” he said.

--Mary Caffrey

References, Artificial Pancreas

1. Mattina C. Infographic: hybrid closed-loop insulin delivery systems—outcomes and outlooks. The American Journal of Managed Care® website. ajmc.com/newsroom/infographic-hybrid-closed-loop-insulin-deliverysystems-outcomes-and-outlooks. Published June 16, 2017. Accessed July 21, 2017.

2. Del Favero S, Boscari F, Messori M, et al. Randomized summer camp crossover trial in 5-to 9-year-old children: outpatient wearable artificial pancreas is feasible and safe. Diabetes Care. 2016;39(7):1180-1185. doi: 10.2337/dc15-2815.

3. Stewart ZA, Wilinska ME, Hartnell S, et al. Closed-loop insulin delivery during pregnancy in women with type 1 diabetes. N Engl J Med. 2016;375(7):644-654. doi: 10.1056/NEJMoa1602494.

4. Garg SK, Weinzimer SA, Tamborlane WV, et al. Glucose outcomes with the in-home use of a hybrid closed-loop insulin delivery system in adolescents and adults with type 1 diabetes. Diabetes Technol Ther. 2017;19(3):155-163. doi: 10.1089/dia.2016.0421.

5. Kovatchev B, Peiyao C, Anderson SM, et al. Feasibility of long-term closed-loop control: a multicenter 6-month trial of 24/7 automated insulin delivery. Diabetes Technol Ther. 2017;19(1):18-24.

doi: 10.1089/dia.2016.0333.

References, CGM Debate

1. Medicare announces criteria covering Dexcom G5 Mobile CGM for all people with diabetes on intensive insulin therapy [press release]. San Diego, CA: Dexcom; March 24, 2017. https://www.dexcom.com/news/medicareannounces-criteria-covering-dexcom-g5-mobile-cgm-for-all-people-withdiabetes-on-intensive-insulin. Accessed July 20, 2017.

2. Beck RW, Riddlesworth T, Ruedy K, et al; DIAMOND Study Group. Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial. JAMA. 2017;317(4):371-378: doi:10.1001/jama.2016.19975.

3. New study shows adults with type 1 and type 2 diabetes on multiple daily injections (MDI) benefit from CGM [press release]. San Diego, CA: Business Wire; June 9, 2017. http://www.businesswire.com/news/home/20170609005161/en/Study-Shows-Adults-Type-1-Type-2. Accessed June 11, 2017.

4. Manning JP, Halford J, Sulik B, Sulik M, Parkin CG, Liljenquist DR. Use of continuous glucose monitoring is acceptable and potentially beneficial in older T2DM patients treated with basal insulin therapy: a pilot study. Infusystems Intl. 2014;13(4):35-42.

References, Technology at AADE

1. Caffrey M. Rule would limit digital providers to makeup sessions when Medicare launches DPP in 2018. The American Journal of Managed Care® website. ajmc.com/newsroom/rule-would-limit-digital-providers-to-makeup-sessions-when-medicare-launches-dpp-in-2018. Published July 14, 2017. Accessed August 8, 2017.

2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. CDC website. cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Published July 18, 2017. Accessed August 8, 2017.

3. Abbott receives FDA approval for the FreeStyle Libre ProSystem, a revolutionary diabetes sensing technology for healthcare professionals to use with their patients [press release] Abbott Park, IL: PR Newswire; September 28, 2016. prnewswire.com/news-releases/abbott-receives-fda-approval-for-the-freestyle-libre-pro-system-a-revolutionary-diabetes-sensing-technology-for-healthcare-professionals-to-use-with-theirpatients-300335325.html. Accessed August 8, 2017.

4. Caffrey M. Medicare issues rules for CGM coverage—no smartphones allowed. The American Journal of Managed Care® website. ajmc.com/newsroom/medicare-issues-rules-for-cgm-coverage-no-smartphones-allowed. Published March 28, 2017. Accessed August 8, 2017.

5. MannKind and One Drop partner to launch the A-ONE clinical trial [press release]. Valencia, CA, and New York, NY: Globe Newswire; August 7, 2017. globenewswire.com/news-release/2017/08/07/1081103/0/en/MannKindand-One-Drop-Partner-to-Launch-the-A-ONE-Clinical-Trial.html. Accessed August 8, 2017.

6. WellDoc, American Association of Diabetes Educators (AADE) partner to Incorporate AADE diabetes self-management education curriculum into the BlueStar digital therapeutic platform [press release]. Columbia, MD: Globe Newswire; January 4, 2017. globenewswire.com/news-release/2017/01/04/903158/0/en/WellDoc-American-Association-of-Diabetes-Educators-AADE-Partner-to-Incorporate-AADE-Diabetes-Self-Management-Education-Curriculum-into-the-BlueStar-Digital-Therapeutic-Platform.html. Accessed August 8, 2017.

7. Proteus Digital Health website. proteus.com. Accessed August 8, 2017.

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