As you all know, we were in Boston attending the 75th annual ADA Scientific Sessions last week. At the heart of this whole gathering is of course the science -– the loads of new studies completed around the country and the world over the past year that are now ready to be presented to medical peers.
A few of the big topics that were common themes or had multiple presentations this year included:
Initial results of the much-anticipated FLAT-SUGAR trial by Dr. Irl Hirsch of the University of Washington were announced.
As you may remember, Hirsch is a type 1 himself and huge proponent of looking at glycemic variability independent of A1c to evaluate health outcomes of PWDs (people with diabetes).
He’s the researcher who shined the spotlight on the importance of standard deviation of glucose levels (a measure of how much they swing), which was also the focus of this FLAT-SUGAR trial (which stands for Fluctuation Reduction with Insulin and GLP-1 Added Together).
In a nutshell, researchers believe that glucose variability may have a much bigger impact on diabetes health outcomes than previously recognized, and possibly be even more meaningful t
han the "gold standard" A1c test. So this 10-month long multi-center study was designed to determine if they could decrease glycemic variability while keeping the same A1c levels in patients with insulin-requiring type 2 diabetes.
So far they've looked at 102 adults with type 2 diabetes aged 40-75 who were on either basal insulin or metformin, and then assigned to add either Byetta or rapid-acting insulin. CGM was used to monitor BG levels, which is a step forward all on its own because more researchers are now using that tool to keep tabs on real-time data during their studies.
The two trial groups were targeted to achieve the same final A1c levels, while researchers watched carefully for different levels of glycemic variability.
Results so far show that yes -- you can reduce glucose variability while keeping A1cs similiar.
Hirsch reported that the initial study is not large enough to provide a final answer regarding the role of glycemic variability in glucose control, but it should pave the way for more long-term definitive trials that also explore this issue in a broader sense for all people with diabetes.
The Access Issue
A common theme throughout the conference was inadequate access to care, medications, and education. There was a lot of talk about hypoglycemia and glucose variability overall (see Hirsch's work above) that led into more talk about how accessing meters, strips and CGMs, and affordable medications can help reduce the risk of hypos and also hyperglycemia.
CMS Competitive Bidding: Data presented at ADA highlighted the unintended consequences of the Centers for Medicare and Medicaid Services (CMS) competitive-bidding program that began in 2011 and has severly limited access to diabetes supplies in recent years. The National Minority Quality Forum presented a late-breaking study showing that PWDs suffering from reduced access to needed D-supplies were more likely to be hospitalized or even die from D-related causes. CMS data from 2009 to 2012 shows the number of beneficiaries with only partial access to necessary D-supplies increased by 23% as a result of competitive bidding changes, and the number of deaths was twice as high compared to the rest of the Medicare market; nearly 1,000 patients were admitted to the hospital at a cost of $10.7 million.
Medicare on CGM: On Monday night at the TCOYD / diaTribe forum, CGM Access for older PWDs on Medicare was also a key discussion topic; it was dubbed "morally indefensible" that Medicare doesn't cover this technology. In fact, on the final morning of the conference, the ADA's chief medical officer Bob Ratner said, "CMS has a real awakening coming" on this issue, as advocates from across the diabetes community are pushing for legislative and policy change. A lot of research presented at the Scientific Sessions -- from the above-mentioned competitive-bidding data, to studies on hypoglycemia risk and hospitalization and how better D-tech use helps people and reduces overall cost -- can all play into this advocacy and be used as ammunition in this fight for better access.
Education Needs: The ADA teamed up with two other big diabetes orgs (the American Association of Diabetes Educators and the Academy of Nutrition and Dietetics) to publish a joint statement about the need for better education and support for PWDs, backed by new data showing that less than 7% of PWDs are referred to educators. The three orgs have created a new "algorithm" calculating when PWDs should be referred to educators, such as post-diagnosis for T2s; annually; and if there are any complicating factors or big life transitions. Nice to know that these D-groups are including patient engagement and psychosocial factors into their algorithm to determine when these referrals should happen, too!
T2 Meds and Heart Health
The effect of glucose-lowering medications for type 2 diabetes on cardiovascular health is an ongoing concern. A bevy of new studies all brought good news:
- DPP-4 inhibitors were shown not to could interfere with the efficacy of ACE inhibitors’ (blood pressure-lowering pills) ability to protect high-risk diabetes patients from cardiovascular events. This study in over 5,000 patients found no link between DPP-4 inhibitors and risk of (cardiovascular disease) risk in patients treated with both types of drugs.
- Results of the TECOS (Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin) study were presented. Sitagliptin is the DPP-4 inhibitor otherwise known as Januvia from Merck. The trial met its goal endpoint of “non-inferiority,” meaning there was no increase in hospitalization for heart failure in patients using Januvia vs. a placebo. Very good to know!
- Similarly separate study results of the EXAMINE trial showed that use of DPP-4 inhibitor alogliptin (U.S. trade name Nesina, from Takeda) had no association with acute cardiovascular events or cardiac hospitalizations and procedures such as stinting.
- A third study found that the DPP-4 inhibitor Vildigliptin (trade name Galvus) did a much better job than sulfonylureas (another class of inexpensive T2 D-drugs) of protecting patients against the risk of microvascular diseases, such as neuropathy and retinopathy.
- And a fourth study called SAVOR showed that the DPP-4 inhibitor Saxagliptin does not cause increased incidence of cancer or mortality over 2.1 years of follow up with patients (yay!).
- Meanwhile, sulfonylureas were also shown to be heart-safe, in a large “meta-analysis” that found no association between them and CVD risk, including mortality, myocardial infarction (aka heart attack) and stroke (more yay!).
- A study in seniors with diabetes found that the SGLT-2 inhibitor Dapagliflozin (trade name Farxiga, from a new class of drugs that sloughs off glucose through the urine) did not increase CVD risk in elderly people with diabetes after 4-5 years, but it did lower blood glucose levels as promised.
- And speaking of SGLT-2 drugs, results of two Phase 3 trials were unveiled Saturday (ClinicalTrials.gov IDs: NCT01646320 and NCT01619059). Weirdly, these studies tested “triple therapy” of the SGLT-2 drug dapagliflozin with saxagliptin (a DPP-4 inhibitor, trade name Onglyza) and metformin. This is presumably leading to yet another combo-drug offering for type 2 patients, in this case a “triple fixed dose” from Farxiga producers Bristol Myers-Squibb.
Artificial Pancreas Progress
- One study looked at “normal-life use of the artificial pancreas in adolescents” by allowing young people with well-controlled diabetes to use an AP system outside the clinic for seven days running under normal life conditions; it was shown to be safe and effective, without increasing the risk of hypoglycemia
- Another study conducted at a summer diabetes camp compared glucose regulation using just an insulin pumps to use of a “bi-hormonal” bionic pancreas (that administers both insulin and glucagon) in kids ages 6-11. The bionic pancreas option was shown to be safer and more effective than the insulin pump alone over 5 days, during which campers chose their own meals and took part in all camp activities. The bionic pancreas both reduced the mean glucose and the amount of time that campers were hypoglycemic.
- A long-term, six-center trial looked at 30 adults with type 1 diabetes using a closed-loop system in real-world settings in the US and Europe, and alos found the system both safe and effective; it reduced the duration of hypoglycemia and increased time in target range during a four-week use period.
- Two hormones are better than one, right? A true artificial pancreas would deliver both insulin, which lowers blood glucose levels, and glucagon, which raises blood glucose levels. These two studies compared a dual-hormone delivery system, a single hormone artificial pancreas and a conventional insulin pump in outpatient settings, over two and three nights. The dual-hormone AP was most effective at improving glucose control in patients ages 9 to 70, with greatly reduced episodes of hypoglycemia, compared to the other systems.
- During a symposium on closed loop tech, Dr. Stayce Beck with the FDA talked about how excited and supportive the regulatory agency is about AP research. It was great to hear that, but even moreso she called out diabetes device manufacturers at one point saying they need to do adult and kid studies on this next-gen technology all at the same time; that there isn't any data showing it's easier to get adult approval first, and then study the pediatric market afterward. (Hint hint, Medtronic and Animas -- both working on closed loop systems but still have not received pediatric designation for their existing pump-CGM combo devices.)
- Interestingly, we heard Dr. Ed Damiano say during his presentation about the Bionic Pancreas that in the coming months they'll be looking beyond the dual-hormone pump with glucagon and actually exploring how effective their system is with only insulin. They'll be starting more studies by late year and into the first half of 2016.
Faustman and Cure Research
Among the myriad ADA abstracts were dozens delving into "cure" research -- from prevention, encapsulation and islet transplants and beta cell regeneration.
Dr. Denise Faustman presented and announced that the next phase of her vaccine research is now starting. This five-year study will happen at Massachusetts General Hospital where she practices, and include as many as 150 people between the ages of 18-65. Her results showcase the discovery that long-term diabetics can have persistent existence of C-peptide (insulin secretion from the pancreas) for decades after diagnosis. As she told us in our interview earlier this year, that's Faustman's rationale for doing some of the first immuno-intervention trials in people with longtime T1D, not just those with new-onset diabetes.
Behavorial and Psychosocial Stuff
We were excited to see more focus on mental health and behavioral outcomes at the ADA conference, although it remains an issue that still needs more attention. A new partnership between ADA and the American Psychology Association will focus on training psychologists to deal with diabetes issues, helping to make this more of a focus.
ADA's head of Healthcare and Education Dr. Dave Marrero (who's a fellow a type 1 and is part of Mike's Adult D-Community in Indiana), emphasized the need for more focus on these topics. He pointed out that only 3% (17 out of 571) of the ADA grants in 2015 touched on behavioral and mental health, and less than 1% of the National Institute of Mental Health (NIMH) grants have diabetes in the title. In Marrero's words, "we are failing terribly." He invited researchers to start focusing on this area, and also encouraged the diabetes medical community to include more patient voices in the research process (!)
Given this year's ADA theme marking the organization's 75th year, there were many looks back on how far we've come. The main conference center lobby had a pretty impressive exhibit on diabetes care through the decades, highlighting milestones in each of those 10-year spans. Weaved in through most of the five-day conference, you could find references to D-history and some interesting anaylsis of research that changed the game -- from development of new medications and technology since the "diabetes dark ages in the 70s" to the landmark Diabetes Control and Complications Trial (DCCT) in 1993.
On Tuesday morning, a two-hour session that Mike attended explored 50 Years of Diabetes and included some longtime influencers in the diabetes world, including renowned endo Dr. Fred Whitehouse from Detroit, who worked directly with the legendary Dr. Eliot Joslin back in the late '40s right there in Boston (back then, it wasn't yet known as the Joslin Diabetes Center).
Honestly, being in a room with about 70 veteran type 1s -- one of them being diagnosed at age 8 almost eight decades ago! -- was the most emotional part of the conference for Mike, he says. A big group of Joslin medalists gathered for the session before heading over to the Joslin Diabetes Center for a reception. Bob Ratner of the ADA pretty summed it up beautifully with this line: "THAT is why we do this diabetes research."
Treatment Using Phones, Web & Video
There appeared to be a LOT more content this year around how to use technology successfully to help patients with their self-care. A few of those sessions included:
- The Alive-PD study at UC Berkeley, a randomized, controlled trial that tested whether a fully-automated algorithm-driven intervention can lower BG levels among pre-diabetics over six months. The solution used was developed by NutritionQuest and included weekly emails to users with information and personalized recommendations on food, exercise, and “motivational interaction.” Users could also access a web tool for further interaction and tracking, plus a mobile app for networking and social support. They could also opt to receive print materials and reminder phone calls if desired. With all that support, it’s no surprise that the 340 participants achieved statistically significant improvements in weight loss and blood glucose levels. So yes, a program like this can be very helpful!
- Another study demonstrated how Drag n’ Cook, a meal planning app from Joslin’s Asian Diabetes Initiative, helped Asian American participants make their own traditional recipes healthier. Participants had to cook at home at least three times a week, input recipes, and attend three focus groups. The app then made suggestions for healthy modifications. Results showed that using the app helped participants “greatly improve their diets by lowering sugar, calories, total fat, cholesterol and sodium intake.” (We can’t help wondering, though, if attending those in-person focus group was at least as influential as using the app?)
- Can depression be successfully treated using phone calls and video-based therapy? That was the focus of this New York-based study of 392 PWDs identified to be at risk for depression, stress, or anxiety. An 8-week, 16-session program was delivered remotely via phone or video by a therapist trained in cognitive behavioral therapy and a behavioral health coach. Results showed that the more pain, the more gain. In other words, those who were most depressed achieved the greatest improvements in reducing depression, anxiety and stress, as well as improving diabetes self-management.
... and of course the sessions on patient use of technology that we mentioned in the close of our product coverage yesterday (behavioral science), in which a number of folks from the DOC (Diabetes Online Community) presented, including myself. The feedback I got on my own presentation, Social Media: Part of the Diabetes Prescription? was pretty incredible.
Kudos to ADA for including us!