People with type 1 diabetes (T1D) have to live with it 24 hours a day, 7 days a week, 365 days a year. But this year’s American Diabetes Association’s (ADA) Scientific Sessions brought hope and inspiration to people living with T1D. JDRF was there at the ADA’s Scientific Sessions—which took place June 22 to 26 in Orlando, Florida—and highlighted the JDRF-funded and supported research under way, encompassing breakthrough clinical trials and significant research studies that are paving the way to novel and emerging treatments for T1D.
SGLT Inhibition: It’s Not Just for Type 2 Anymore
JDRF Research Area: Glucose Control
SGLT inhibition has been approved for type 2 diabetes—and not T1D—but that’s about to change. Dapagliflozin (Farxiga®/Forxiga®) and sotagliflozin (Zynquista™) have been submitted for approval for T1D, to be used in addition to insulin therapy to improve glucose control. At ADA’s Scientific Sessions, dapagliflozin—presented by Paresh Dandona, M.D., and Chantal Mathieu, M.D., Ph.D.—and sotagliflozin—presented by John Buse, M.D., Ph.D.—both reduced HbA1c, and also led to a reduction in insulin doses and an increased time-in-range. But both showed an increase in DKA, a life-threatening condition caused when insulin is too low. Furthermore, DKA did not come with the hallmarks of it—hyperglycemia. There was a lot of discussion on what to do about this, and patient and physician education was one of the aims of bringing this to the T1D community. An additional SGLT-2 inhibitor, empagliflozin (Jardiance®), demonstrated that in phase III trials in T1D adults, a lower dose of the drug prevented DKA while not compromising on the glycemic and metabolic benefits.
JDRF Leadership: JDRF was critical in bringing sotagliflozin to the T1D community. In 2015, JDRF jointly funded a phase II clinical trial to test sotagliflozin in young adults with elevated HbA1c. This and other clinical trials showed several benefits of the drug, above and beyond reductions in HbA1c, such as time in range, body weight and blood pressure, without increasing hypoglycemia.
Clinical Trial in Beta Cell Replacement Therapy
JDRF Research Area: Beta Cell Replacement
ViaCyte’s lead candidate for beta cell replacement therapy is the PEC-Encap combination, consisting of pancreatic progenitor cells (PEC-01) encapsulated in a delivery device called the Encaptra® Cell Delivery System. This presentation was the first description of data from the clinical trial that tested the safety and tolerability of PEC-Encap in 19 patients, and the outcomes were very exciting. The results showed that when engraftment occurs, viable mature insulin-expressing islet cells were formed. The cells can also persist for long durations without the need for immunosuppression. Wow!
JDRF Leadership: JDRF has been funding ViaCyte since 2011, as part of its Industry Discovery and Development Program (IDDP). There are now six companies testing their beta cell replacement therapies through IDDP, with the goal of delivering insulin independence without immunosuppression to the diabetes community.
Combination Immune Therapy: ATG-GCSF Clinical Trial
JDRF Research Area: Immune Therapies/Beta Cell Regeneration
Michael Haller, M.D., of the University of Florida, unveiled results of a clinical trial that tested Thymoglobulin®, or anti-thymocyte globulin (ATG), and Neulasta®, an immune activator, also called GCSF—both of which are FDA approved agents—to see if the combination could preserve beta cell function in new-onset T1D. The study found that a short course of low-dose ATG did preserve beta cell function and improved insulin production throughout the entire one-year study period. More so, the people who got ATG or the ATG+GCSF combination had significantly lower HbA1c than people who were given a placebo. These results suggest that ATG, alone or in combination, should be considered as a potential means of slowing T1D progression and preserving beta cell mass. More clinical trials are to come!
JDRF Leadership: Dr. Haller received an early career grant from JDRF that provided funding to complete the initial pilot studies of ATG and GCSF in T1D, which laid the groundwork for the larger ATG-GCSF combination trial.
Medtronic 670G in Children
JDRF Research Area: Artificial Pancreas
The Medtronic 670G was approved in 7 to 13 year olds on Thursday, and I got the chance to hear firsthand about the clinical trial that convinced the FDA to supplement its approval. The 670G is an artificial pancreas system, which monitors glucose levels and automatically provides the right amount of insulin through a pump. It is designed to operate in closed-loop mode, but can also be used in manual (open-loop) mode. In the children’s clinical trial, presented by Anirban Roy, Ph.D., of Medtronic, the 670G showed significant reduction in time in hypoglycemia, increased time in target range and lowered HbA1c when in closed-loop mode. What’s more, closed-loop mode made waking up in range far more likely. That’s a real benefit for children and their parents who want to sleep through the night with peace of mind and not be worried about overnight hypoglycemia. Like the previously approved 670G system in adults, the pediatric product requires bolus insulin dosing for meals.
JDRF Leadership: JDRF launched the Artificial Pancreas Project in 2006, leading efforts to accelerate the development of artificial pancreas systems, and working with the FDA to pave a clear pathway to regulatory approval.
JDRF Research Area: Prevention
The TEDDY study aims to identify environmental triggers for T1D, and investigators working on the study provided an update on their findings. Jeffrey Krischer, Ph.D., from the University of South Florida, has results suggesting that T1D is a heterogeneous disease and that there is a relationship between age of T1D onset, genetics and the type of autoantibodies that appear first. Dr. Krischer showed that children who develop islet autoimmunity early tend to develop insulin autoantibodies first and progress faster to T1D, while those who develop islet autoimmunity later in childhood tend to develop GAD autoantibodies and progress more slowly. Dr. Krischer closed with an intriguing slide suggesting that innate immunity may play a role in T1D, but cautioned that association is not prediction.
JDRF Leadership: JDRF has supported TEDDY since its inception in 2004, and is currently funding Dr. Krischer for follow-up of children taking part in the study.
Link Between Hypoglycemia and Abnormal Heart Rhythms
JDRF Research Area: Complications
Simon Fisher, M.D., Ph.D., of the University of Utah, presented fascinating data on the link between hypoglycemia and heart failure. He found that those who have hypoglycemia a number of times develop cardiac arrhythmias, and if they have severe hypoglycemia again, it could lead to sudden death. However, putting a beta blocker—an oral medicine that is used for high blood pressure—in the mix, he was able to ward off death. As he said, though, all of his studies have been in animal models. Humans next?
JDRF Leadership: Dr. Fisher was supported by JDRF since 2001, when he was a postdoctoral fellow at Joslin Diabetes Center. Since then, he has been funded through several grants from JDRF, and is a mentor to JDRF-funded postdoctoral fellows.
New Role for Neutrophils in T1D
JDRF Research Area: Prevention
Manuela Battaglia, Ph.D., from the Ospedale San Raffaele in Milan, Italy, and her colleagues from TrialNet, have found intriguing results regarding the role of a type of immune cell, neutrophils, in the early stages of T1D. TrialNet’s Pathway to Prevention study follows individuals at-risk for T1D and collects samples, allowing investigators to identify triggers and predictors of progression to T1D. Using samples collected by TrialNet, Battaglia has found that there is, in the blood, a reduced number of circulating neutrophils during progression to T1D. The lower the neutrophil count in an individual, the more they are likely to get T1D and lose beta cell function faster. What’s more, she discovered that neutrophils are abnormal in at-risk autoantibody-negative people! Future work will be focused on understanding why neutrophils are predictive of T1D and whether targeting neutrophils can slow or stop progression of T1D.
JDRF Leadership: Dr. Battaglia has received JDRF funding since 2008, when she was an early career scientist at her organization. She has received two more grants to study the role that immunological cells can contribute to T1D.
JDRF and its Partners Win Top Honor for Hurricane Relief Work
JDRF is honored to receive this award, along with the founding members, the ADA and Insulin for Life USA, and many other organizations that have been instrumental, in coordinating the Diabetes Emergency Response Coalition, which provides critical diabetes supplies to regions impacted by last Fall’s hurricanes. The Summit Power of A Award is the highest recognition for associations who make exemplary commitments to solving problems and improving world conditions. Well done to the members of the Emergency Response Coalition for this honor!