ADA Recap Series
This article is the first of our three-part ADA Recap Series. Breakthrough T1D was on site in Chicago, IL from June 20-23 for the American Diabetes Association’s (ADA) 85th Scientific Sessions. We’re here to report on the latest-and-greatest type 1 diabetes (T1D) advancements—including many driven by Breakthrough T1D funding. Look out for tomorrow’s article for updates on Cures.
Improving Lives
Breakthrough T1D’s Improving Lives program focuses on devices, insulins, adjunctive therapies, treatments for complications, and psychosocial interventions to improve the health and quality of life of people living with T1D.
Adjunctive therapies and complications
There was significant focus on GLP-1 receptor agonists (GLP-1RAs) and SGLT inhibitors (SGLTi) in reducing long-term complications and improving glycemic control in people with T1D.
GLP-1 receptor agonists
Glucagon-like peptide 1 receptor agonists mimic the hormone GLP-1, which elevates insulin and regulates appetite. Examples include Ozempic® (semaglutide) and Mounjaro® (tirzepatide), which acts on both GLP-1 and a similar target, GIP.
SGLT inhibitors
Sodium-glucose cotransporter inhibitors target kidney cells to prevent them from reabsorbing glucose into the blood so it gets excreted as waste. Examples include Farxiga® and Zynquista®.
While SGLTi and GLP1-1RAs have proven effective for heart and kidney disease in type 2 diabetes (T2D) and in people without diabetes, people with T1D have often been excluded from critical trials. Thanks to years of advocacy and support from Breakthrough T1D, T1D trials are ongoing—and real-world evidence suggests that GLP-1RAs and SGLTi could be impactful in the T1D community as well.
Real-world evidence for GLP-1RA use in T1D
- Presenter: Ildiko Lingvay, M.D.; University of Texas Southwestern
- People with T1D have self-reported that they decided to try GLP-1RAs for weight loss and improved glycemic control.
- Real-world evidence suggests that GLP-1RAs have a clinically meaningful impact on weight and reduced insulin dose.
- While GLP-1RAs are generally safe, some people have stopped use because of gastrointestinal side effects. These side effects are also seen in people with T2D and people without diabetes.
A review of SGLTi and GLP-1RAs in reducing chronic kidney disease (CKD) in T1D
- Presenter: David Cherney, Ph.D.; University of Toronto
- In the EMPA-KIDNEY trial that included non-diabetes participants and people with T1D or T2D, empagliflozin (SGLTi) improved kidney health in people with T1D.
- In the ATTEMPT trial, dapagliflozin (SGLTi) improved time in range (TIR), reduced HbA1c levels, and had positive effects on kidneys in youth with T1D.
- The Breakthrough T1D-funded enrolling phase 3 SUGARNSALT trial is testing whether sotagliflozin (SGLTi) can prevent progression of moderate to severe kidney disease in people with T1D, and it includes careful diabetic ketoacidosis (DKA) risk mitigation strategies.
- The SEMA-AP trial found that semaglutide (GLP-1RA) increases TIR in people with T1D when used alongside an AID system.
- The Breakthrough T1D-funded recruiting phase 2 REMODEL-T1D trial is testing if semaglutide (GLP-1RA) can improve kidney health in people with T1D.
Glucokinase
Glucokinase (GK) is an enzyme in liver cells that works in an insulin-dependent manner to regulate blood sugar. In people with T1D who have little insulin reaching the liver, GK can’t work as normal, contributing to higher blood sugar.
Use of a glucokinase activator for glycemic control
- Presenter: Klara Klein, M.D., Ph.D.; University of North Carolina
- In the phase 1/2 SimpliciT1 study, people with T1D who received the GK activator TTP399 showed improvements in blood glucose with fewer hypoglycemic events.
- A different study found that TTP399 does not increase the risk for DKA.
- These studies were done in collaboration with vTv Therapeutics, a company with funding and support from Breakthrough T1D and the T1D Fund: A Breakthrough T1D Venture. The phase 3 CATT1 study for TTP399 is testing whether it can reduce moderate to severe hypoglycemic events in people with T1D.
Adjunctive therapies and complications highlight: Breakthrough T1D-funded research
Halis Kaan Akturk, M.D. (University of Colorado), Janet Snell-Bergeon, Ph.D., MPH (University of Colorado), and Viral Shah, M.D. (Indiana University) presented findings from the Breakthrough T1D-funded ADJUST-T1D clinical trial, which was recently published in the New England Journal of Medicine Evidence. The trial tested whether semaglutide (GLP-1RA) can improve glycemic and weight outcomes in adults with T1D and obesity who are using an AID system. 36% of people treated with semaglutide met the primary endpoints of TIR greater than 70%, time below range less than 4%, and weight loss of 5% or more compared to the placebo, and the drug was well-tolerated and safe. This trial represents critical evidence for use of a GLP-1RA as a potential way to manage both glycemic control and weight in people with T1D.
Ye Je Choi, MPH (University of Washington) reported on the CROCODILE study, which examined metabolic alterations in kidneys of people with T1D. She observed early structural and metabolic changes in kidneys that occurred before the onset of clinical kidney disease and associated structural damage. Her work could contribute to the development of biomarkers that can help predict the onset of kidney disease in people with T1D before it occurs.
Jeremy Pettus, M.D. (University of California at San Diego) conducted a phase 2 clinical trial to address insulin resistance in people with T1D. External insulin therapy can increase levels of insulin in the blood relative to glucose, which reduces sensitivity and may contribute to cardiovascular disease (CVD). Treatment with the glucagon receptor antagonist volagidemab, which prevents the liver from releasing glucose into the blood, reduces insulin requirements by 15%, resulting in improved glycemic control and insulin sensitivity without changes in bodyweight.
Schafer Boeder, M.D. (University of California at San Diego) worked with Dr. Pettus on a phase 1/2 clinical trial that tested whether the addition of SGLTi to the glucagon receptor antagonist volagidemab can further improve glycemic control in people with T1D. The combination of therapies increased TIR up to 86% from 70% and reduced daily insulin use by 27%. Further research is needed to better understand the safety profile of this regimen.
Justin Gregory, M.D. (Vanderbilt University) worked with Dr. Pettus and Dr. Boeder on the above study. He also presented on the use of GLP-1RAs and dual GLP-1/GIP receptor agonists for reducing complications in T1D.
Key takeaways
Clinical trials with GLP-1RAs and SGLTi are providing encouraging evidence about these therapies’ potential to improve long-term health in people with T1D. Breakthrough T1D is working toward a future where these drugs are an option for people with T1D to better manage their blood sugar and reduce complications.
Devices
Real-world insights from Automated Insulin Delivery (AID) systems
- Presenter: David Maahs, M.D., Ph.D.; Stanford University
- Based on published real-world evidence for AID systems in people with T1D, TIR is increased by an average of eight to 15% from baseline in a range of studies across various systems.
- Youth with T1D have better glycemic control and reduced rates of DKA with AID systems. Those with lower TIR at the start of AID system use see the greatest improvements.
Real-world evidence: iLet Bionic Pancreas AID system
- Presenter: Steven Russell, M.D., Ph.D.; Beta Bionics
- The iLet Bionic Pancreas contains a continuously adapting algorithm that automatically determines insulin doses. No carbohydrate counting is required, and meals are only announced as breakfast, lunch, and dinner.
- Data was collected from 16,000 users over two years.
- Users achieved an average HbA1c level of 7.3%, down from 8.9%. This is accompanied by low rates of hypoglycemia and significantly improved self-reported quality of life.
Continuous ketone monitoring: Innovations and clinical applications
- Presenters: Ketan Dhatariya, MBBS, M.D., Ph.D. (Norfolk and Norwich University Hospitals), Lori Laffel, M.D., MPH (Harvard University), Jennifer Sherr, M.D., Ph.D. (Yale University), and Richard Bergenstal, M.D. (HealthPartners Institute).
- DKA rates are increasing in the U.S., but mortality rates from DKA are decreasing.
- The history of continuous glucose monitoring (CGM) offers a roadmap for continuous ketone monitoring (CKM) development, showing how early skepticism gave way to broad clinical impact.
- CKM could allow for earlier detection of rising ketones to prevent DKA. CKM also has the potential to identity infusion set failures, be a valuable addition to AID systems, help monitor early-stage T1D, and more.
- Five new studies funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will develop CKM for safe and effective use of SGLTi in T1D.
- Tandem, Beta Bionics, Sequel MedTech, and Ypsomed announced plans to integrate Abbott’s dual glucose ketone sensor into their AID systems.
Making the case for time in tight range
- Presenter: Gregory Forlenza, M.D.; University of Colorado
- Dr. Forlenza presented on the benefits and challenges of time in tight range (TITR), also known as time in normal glycemia (TING), defined as blood glucose levels between 70-140 mg/dL.
- TITR will likely be more clinically beneficial than TIR as fluctuations outside of TITR may be better predictors of complications and offer a better therapeutic window for intervention.
- More research is needed to advance therapeutics that will allow people with T1D to achieve TITR before it can be integrated into clinical decisions.
Devices highlight: Breakthrough T1D-funded research
Erin Cobry, M.D. (University of Colorado) presented the results of a Breakthrough T1D-funded clinical trial evaluating an artificial intelligence-powered AID algorithm designed to not require meal announcements. She showed that this algorithm (used without meal announcements) improved overnight TIR, and provided equivalent daytime TIR, compared to participants’ usual care. A major goal for Breakthrough T1D is to advance AID systems that do not require meal announcements to improve both glucose outcomes and quality of life for people with T1D.
Key takeaways
Devices have transformed how this disease is managed. Systems are becoming easier to use with less user input—and, critically, people with T1D are doing better. This is the dream Breakthrough T1D had when we launched the Artificial Pancreas project 20 years ago. We will continue to drive toward our goal of developing systems that provide superior health outcomes with minimal user burden.
Insulins
Inhaled insulin treatment for youth with T1D
- Presenter: Michael Haller, M.D.; University of Florida
- Afrezza® is an inhaled, fast-acting insulin that has proven to be effective in adults.
- The phase 3 INHALE-1 study examined Afrezza® in youth with T1D. Users report greater treatment satisfaction and no increase in weight compared to injected rapid-acting insulin analogs.
- Afrezza® is safe for youth with T1D. The most common adverse events were pulmonary-related, such as coughing.
Breakthrough T1D’s Improving Lives team making an impact
Courtney Ackeifi, Ph.D., Senior Scientist, hosted an Improving Lives Happy Hour with Breakthrough T1D-funded researcher Jeremy Pettus, M.D. The discussion included research priorities for adjunctive (non-insulin) therapies for people with T1D and their healthcare providers. They also discussed the importance of industry partnerships and the role of Breakthrough T1D in driving these relationships, which can accelerate new T1D therapies toward the clinic.
Dr. Ackeifi also spoke at the ADJUST-T1D trial update, contextualizing the use of adjunctive therapies like GLP-1RAs for superior glucometabolic control in people with T1D.
Look out for tomorrow’s article for an update on Cures research presented at ADA 2025!
