Breakthrough T1D joined thousands within the diabetes community at the American Diabetes Association (ADA) 84th Scientific Sessions. Held June 21–24 in Orlando, FL, scientists presented 190+ studies with Breakthrough T1D funding—at present or in the past—to encompass breakthrough clinical trials and significant research studies that are paving the way to novel treatments and technologies for T1D.
Here is Aaron J. Kowalski, Ph.D., CEO of Breakthrough T1D, with the key takeaways from the conference and below is a written summary of Breakthrough T1D highlights.
Cures
Stem cell-derived islet replacement therapy: Update on Vertex’s VX-880
Breakthrough T1D research area: Cell therapies
Cell replacement therapies, including stem cell-derived islet therapy, were on fire, again, with Vertex Pharmaceuticals once more leading the way in clinical trials. Vertex launched its clinical trial of VX-880, a stem cell-derived islet therapy in T1D for individuals with low blood sugar (called hypoglycemia) unawareness, in combination with immunosuppressive therapy to protect the cells from rejection, in the summer of 2021. Within Parts B and C, 12 participants have received the full, target dose of cells, and the results are remarkable. 11 of the 12 participants have reduced or eliminated the need for external insulin. What’s more, all 3 individuals who received the therapy at least 12 months ago have eliminated hypoglycemic events and are fully off external insulin—meeting the primary and secondary endpoints. There were no significant side effects related to VX-880, and the trial has expanded to enroll 20 more participants, to 37.
In summary: VX-880 has curative potential, with achieving insulin independence, eliminating severe low blood-sugar events, and significantly improving blood-sugar control all within reach.
Breakthrough T1D leadership: Vertex’s phase I/II clinical trial of VX-880 was pioneered by Doug Melton, Ph.D., whose years of Breakthrough T1D-funded research led to successfully transforming stem cells into beta cells in 2014, and a catalytic investment from the T1D Fund: A Breakthrough T1D Venture in Semma Therapeutics—a biotech company founded by Melton to develop a stem cell-derived islet therapy for T1D, which was acquired by Vertex Pharmaceuticals.
Tzield® (teplizumab-mzwv): Additional improvement in Stage 3 T1D
Breakthrough T1D research area: Disease-modifying therapies
Kevan Herold, M.D., presented a secondary analysis of the phase III PROTECT clinical trial. In October 2023, Tzield® (teplizumab-mzwv) showed that it can slow the loss of beta cells and preserve beta cell function in newly diagnosed (stage 3 T1D) children and adolescents ages 8-17. In the present analysis, Tzield® demonstrated that, in addition to slowing down the loss of beta cells in new-onset T1D, it could decrease insulin dose, improve time-in-range, and decrease severe low blood sugar events. This reinforces our commitment to supporting therapies that preserve beta cells at onset, which is important for the prevention of complications and improvement in new-onset clinical factors.
Breakthrough T1D leadership: Dr. Herold has been supported by Breakthrough T1D since the late 1980s. In his research, he showed that he could prevent autoimmune diabetes with an immune-modifying antibody (which later became a humanized version) and was the lead on the clinical trial that demonstrated that Tzield could delay the onset of T1D in people almost certain to develop the disease. In November 2022, Tzield was approved by the FDA to delay the onset of the disease (Stage 3) in at-risk (Stage 2) individuals ages 8+.
First international consensus monitoring guidance
Breakthrough T1D research area: Early detection
Breakthrough T1D spearheaded the first internationally agreed-upon monitoring guidance for anyone who tests positive for T1D autoantibodies. These provide guidelines for monitoring children, adolescents, and adults who test positive, along with recommended monitoring frequencies and actions for healthcare professionals when the risk of progression toward symptomatic T1D is high. The guidance also includes recommendations for educational and psychosocial support for positive T1D antibody individuals, including their families and caregivers.
2+ T1D-related autoantibodies—antibodies that are directed toward your own body—means you have an almost 100% chance of developing T1D in your lifetime.
Breakthrough T1D leadership: Until now, there were no monitoring guidelines for individuals who tested positive for T1D autoantibodies. But, for the first time, individuals, families, and healthcare professionals have concrete next steps to monitor early-stage T1D progression and catch symptoms early to prevent DKA. This will reduce DKA at diagnosis and identify autoantibody-positive individuals to take part in preventive treatment or clinical trials. This is a landmark publication.
Diabetic ketoacidosis (DKA) is a life-threatening complication, typically due to a shortage of insulin in the body, causing symptoms like dehydration, nausea and vomiting, confusion, and difficulty breathing. Approximately one-third of people in the U.S. present with DKA at the time of T1D diagnosis.
Improving lives
AID technology updates
Breakthrough T1D research area: Artificial pancreas
A ton of presentations focused on the artificial pancreas, or automated insulin delivery (AID), systems. The Medtronic 780G was tested in high-risk youth with T1D, with 80 participants aged 7-25 years; 75% of whom face economic deprivation. Participants saw an average HbA1c reduction of 2.5% (from an average baseline HbA1c of 10.5% to 8%), improvement in time-in-range, and a reduction in low blood sugar events, and there were no incidences of DKA or severe hypo in the AID group. Tandem Mobi had high rates of satisfaction with the system, with the vast majority of respondents (86%) saying they were satisfied or very satisfied. Additionally, 86% of respondents agreed or strongly agreed that Tandem Mobi improved their quality of life. These indicate high real-world satisfaction with Tandem Mobi among early pediatric and adult adopters. Sequel Med Tech twiist AID system, which was FDA-cleared for people with T1D aged 2+ in March 2024, uses the DEKA Loop algorithm, which is based on the Breakthrough T1D-funded FDA-approved Tidepool Loop. This twiist system is expected to launch at the end of 2024.
Breakthrough T1D leadership: In 2005, Breakthrough T1D launched the Artificial Pancreas Project, a multi-million-dollar, multi-year initiative to accelerate the development of systems for automated blood sugar control. The Artificial Pancreas Project would go on to fund more than 150 grants, including 50+ clinical trials, funded by Breakthrough T1D and backed by the Breakthrough T1D Artificial Pancreas Consortium, to make the artificial pancreas system a reality.
“I think [Breakthrough T1D] got us here a lot faster than we could have any other way.”
Francine R. Kaufman, M.D., Chief Medical Officer, Senseonics
Former CMO and Vice President, Medtronic Diabetes (2012-2018), who launched the first artificial pancreas system in 2016
ADA Recipient, 2024 Lois Jovanovic Transformative Woman in Diabetes Award
GLP-1 treatments: Weight loss for T1D?
Breakthrough T1D research area: Glucose control
There is increasing interest in the off-label use of glucagon-like peptide 1 (GLP-1) treatments for weight loss in people with T1D, given that more than two-thirds of people with T1D in the U.S. are overweight or obese. Presented at ADA, the T1D Exchange survey data found that almost 7% of individuals with T1D reported using a GLP-1 therapy, with 65% of people using semaglutide (Ozempic® and Rybelsus® for T2D and Wegovy® for weight loss) and 17% of people using tirzepatide (Mounjaro® for T2D and Zepbound™ for weight loss). To verify the effectiveness and safety profile of this drug class in people with T1D, a retrospective study and a prospective study were presented at ADA. In a retrospective study, those on tirzepatide had 21% of weight loss over one year, with significant blood-sugar improvements. A prospective clinical trial of GLP-1 treatments (semaglutide or tirzepatide) in overweight or obese individuals with T1D showed that it could lead to significant improvements on body weight and HbA1c.
Breakthrough T1D leadership: Breakthrough T1D funded copious research in the 1980s through today to understand the role of glucagon and GLP-1 in T1D. Work revealed that GLP-1 encourages the release of insulin from the pancreas and reduces the release of glucagon, and clinical trials demonstrated that it was effective in treating T2D, eventually leading to its approval in 2005. There are now seven GLP-1 medicines on the market
Correlation between time-in-range and diabetic eye disease
Breakthrough T1D research area: Complications
Using continuous glucose monitoring (CGM) data, the Virtual DCCT Project successfully reproduced HbA1c outcomes in the original DCCT trial. The study found that decreased time-in-range was associated with increased risk for diabetic eye disease. This study reflects continued momentum to validate time-in-range as a primary endpoint in clinical trials.
The Diabetes Control and Complications Trial (DCCT) was a major clinical study involving almost 1,500 participants, ages 13-39, with T1D, conducted from 1983 to 1993. The study compared the effects of standard vs. intensive control of blood sugar on the complications of diabetes. The results showed that intensive blood sugar control reduces the risk of eye disease by 76%, kidney disease by 50%, and nerve disease by 60%.
Breakthrough T1D leadership: Breakthrough T1D has supported eye disease research since its beginning, and has driven discoveries that have reduced the risk of blindness by 95%, including laser therapy and anti-VEGF treatments.
SGLT inhibitors in adolescents with T1D
Breakthrough T1D research area: Complications
In the ATTEMPT (Adolescent T1D Treatment with SGLT2i for hyperglycEMia & hyperfilTration) trial, researchers evaluated the impact of the SGLT inhibitor, dapagliflozin (Farxiga®/Forxiga®), versus a placebo, in combination with insulin therapy, in adolescents with T1D, to find if it can improve kidney function. Findings from the Breakthrough T1D-funded clinical trial showed that a low-dose SGLT inhibitor could improve kidney function and blood-sugar management. There were no significant differences in adverse events, elevated ketone levels, and low blood sugar events. Overall, these results corroborate findings from previous studies in the adult population, which have demonstrated that there are positive kidney effects of SGLT inhibitors, affecting many other pathways to confer multiple benefits.
Breakthrough T1D leadership: In addition to eye disease research, Breakthrough T1D has supported kidney disease research from the beginning. We evaluated the role of puberty in diabetic kidney disease in the early 1990s and found that it played a major role in the development of diabetic kidney disease, where pubertal changes led to increased insulin resistance, rapid kidney growth, and increasing numbers of people being overweight or obese.
Psychosocial screening tools
Breakthrough T1D research area: Behavioral health
There are many ways that T1D can affect people’s social, mental, and emotional well-being, known collectively as psychosocial health, and many Breakthrough T1D-funded researchers presented on psychosocial issues, including Jessie Wong, Ph.D., Holly O’Donnell, Ph.D., and, in place of Jeffrey Gonzalez, Ph.D., Elizabeth Beverly, Ph.D. In addition to diabetes distress, T1D brings about an increased risk of depression, anxiety, executive function, and other psychosocial challenges. Fortunately, there are screening tools to identify who needs help, of varying reliability and validity. But the conclusion: Increase the number of qualified behavioral health professionals with training in T1D.
Breakthrough T1D leadership: Since the Breakthrough T1D Psychosocial Health Program was started in 2018, we have trained 24 psychologists, who have developed expertise in addressing the unique needs of people impacted by T1D and awarded grants of more than $30 million to address the psychosocial challenges of the condition.
You can view all of the oral and poster presentations on the Diabetes journal website.
You can view all of the oral and poster presentations on the Diabetes journal website.
