The short version

Breakthrough T1D’s newest publication outlines what the future of beta cell replacement therapies looks like—and how we can make these therapies a reality for everyone with type 1 diabetes (T1D) who wants them through innovative clinical trial design and expanding the pool of eligible trial participants.

Breakthrough T1D, in collaboration with other leading experts in the field, recently published an article titled “Future Directions and Clinical Trial Considerations for Novel Islet β-Cell Replacement Therapies for Type 1 Diabetes” in the journal Diabetes. Breakthrough T1D Research and Advocacy staff who contributed to the publication include Sanjoy Dutta, Ph.D., Chief Scientific Officer, Esther Latres, Ph.D., Vice President of Research, and Marjana Marinac, Pharm.D., Associate Vice President of Regulatory Affairs.

Beta cell replacement therapies have the potential to cure type 1 diabetes (T1D) by removing the need for external insulin. While donor islet transplantation can result in insulin independence and results from early trials with manufactured islets are encouraging, people with T1D need better tools and therapies. This publication serves as a roadmap for the entire field—including researchers, product developers, industry, regulators, clinicians, and people with T1D—to address these needs and ensure that beta cell replacement therapies can get to people with T1D as quickly and safely as possible.

Read on to learn more about what the future of beta cell replacement therapies looks like.

Where we are now

People living with T1D depend on external insulin to manage their condition throughout their lives. Despite advancements in diabetes technology, such as continuous glucose monitors (CGMs) and automated insulin delivery (AID) systems, most people with T1D are unable to achieve blood sugar targets, rendering them at a higher risk for complications, reduced quality of life, and lower life expectancy.

 It’s simple: we need to do more for the T1D community.

One promising avenue to meet these needs is through cell replacement therapy. Lantidra®, the first FDA-approved donor-derived islet replacement therapy for T1D, has proven to be safe and effective in eliminating severe hypoglycemia, providing insulin independence, and improving quality of life. However, this therapy is limited to people with severe hypoglycemia and requires immunosuppression to prevent rejection of the transplanted cells, which can have side effects. Even more, these donor-derived islets are in limited supply.

Alternative beta cell replacement therapies are emerging—and we can no longer limit their development to people experiencing severe hypoglycemia.

Developing cell therapy strategies to meet unmet needs of the T1D population

Breakthrough T1D’s vision for the T1D community includes beta cell replacement therapies with no immunosuppression that are available to everyone who wants them. We are committed to making this a reality through our Project ACT (Accelerate Cell Therapies) initiative, which will accelerate the development of these therapies to achieve our vision as quickly as possible.

We are entering an exciting era of beta cell replacement. Emerging therapies are addressing challenges such as cell source and scalability, resulting in the development of islets derived from sources other than donors, including manufactured islets and porcine islets. Up-and-coming therapies are also testing different transplantation sites, methods of delivery, and cell protection strategies to prevent immune rejection with the fewest side effects possible (and ideally no immunosuppression). Learn more about what scientists are doing to optimize beta cell replacement therapies.

Breakthrough T1D’s continuous support of many of these therapies, such as Vertex’s manufactured islet therapy zimislecel, has been critical to accelerating them through the clinical pipeline. Explore emerging beta cell replacement therapies in clinical trials now—and see how Breakthrough T1D’s commitment to these therapies helped make this possible.

When successful, the advent of new, safe, scalable, and effective beta cell replacement therapies will provide the T1D community with options. As these therapies are moving their way through the pipeline, we need to ensure they are being studied in a broader T1D population who stand to benefit.

So, how do we make this happen?

The roadmap for emerging beta cell replacement therapies

Expanding the T1D population eligible for beta cell transplantation

Current trials testing beta cell therapies necessitating immunosuppression require participants to have elevated HbA1c levels and recurrent severe hypoglycemic events. This limits the pool of participants to people who meet the requirements and are most likely to benefit, given the side effects associated with chronic, broad immunosuppressants.

Clinical trials for emerging beta cell replacement therapies should broaden eligibility criteria so more people with T1D can participate—and experience the potential benefits. When designing new clinical trials, sponsors and regulators should consider including a broader range of HbA1c levels, clinically important or serious hypoglycemic events, and other complications.

Studies have found that the T1D community is generally open to beta cell replacement therapies as a potential solution to T1D, and people are willing to accept the associated risk versus benefit considerations for the possibility of becoming insulin independent. A Breakthrough T1D assessment also found that physicians are interested in recommending beta cell replacement therapies to people with T1D—especially if they don’t require immunosuppression.

“Clinical trials to support the development of islet cell replacement therapies need to evolve to include a broader representation of people living with T1D who could benefit from these novel therapies. This includes expanding the outcomes used to assess the benefits of cell replacement that reflect how people with T1D feel and function.”

Marjana Marinac, Pharm.D., Associate Vice President of Regulatory Affairs

Placing people with T1D at the center of clinical trial design

The outcomes used to assess the effectiveness of cell therapies currently in clinical trials, including those involving deceased donor islets, are acceptable for emerging beta cell replacement therapies. These include on-target HbA1c levels, absence of severe hypoglycemia, significant reduction or elimination of external insulin, and restoration of the body’s insulin production as measured by C-peptide.

Other endpoints that should be considered include CGM metric targets like time-in-range in addition to person-reported outcomes. Understanding how a beta cell therapy may affect a person’s health-related quality of life—such as diabetes distress, fear of hypoglycemia, or social and family dynamics—will be critically important for calculating the risk to benefit ratio of these therapies.

Read more about why person-reported outcomes are important for cell therapies.

“There are still significant unmet needs in the T1D community. Breakthrough T1D’s roadmap is supported by the assessment of clinically meaningful outcomes and driving research toward solutions that address key factors such as cell sources and protections strategies that will broaden the people with T1D who could benefit from emerging cell replacement therapies.”

Esther Latres, Ph.D., Vice President of Research

Innovative trial designs to accelerate development of cell therapies

Clinical trials for beta cell replacement therapies are generally based on a single-arm, open-label design—meaning there is no placebo group and both participants and researchers know which therapy is being administered. While this design can work for emerging beta cell therapies, single trials with multiple arms testing alternative transplant sites, immune protection strategies, or other methods have the potential to speed up the pace of development.

Similarly, adaptive trial designs use mid-trial interim analyses of study data to inform the remainder of the trial. This helps researchers learn what’s working (or not working) and adjust the design accordingly, with guidance from regulatory agencies, so the rest of the trial is a focused and efficient use of time and resources. Potential interim changes to trial design include reducing the number of participants required, eliminating doses, recruiting people who are most likely to benefit, or stopping the trial outright due to clear success or failure.

By applying guidance in therapeutic development and innovative trial designs to emerging beta cell replacement therapies, we can move early-stage trials along faster, thereby allowing regulators to make decisions sooner. To support quicker trials and reduce the possibility for delays, researchers, developers, and regulators around the world need to work together to achieve convergence on trial populations, endpoints, and innovative designs that will meet regional requirements.

Learning from past successes

People with T1D continue to live with unmet needs with still significant risk for long-term complications, and they need more therapeutic options. Right now, most clinical trials for beta cell replacement therapies requiring immunosuppression are limited to a small portion of the T1D population. This needs to change—especially given the potential for insulin independence. The T1D community must be put first when making decisions about beta cell replacement therapies, and Breakthrough T1D is making sure that this happens.

Adjusting how we approach clinical trials for emerging beta cell replacement therapies will be critical for ensuring we accelerate the research, development, regulatory approval, access and adoption of these novel therapies. Breakthrough T1D successfully accomplished this for AID systems—and we are confident that following a similar roadmap for cell therapies will get us to the finish line, faster.

Curative therapies for T1D are in reach. This roadmap, in conjunction with our Project ACT initiative, is key to bringing beta cell replacement therapies to every person with T1D who wants them.

To make this a reality, everyone needs to work together. As stated in the publication, “This requires a comprehensive strategy and a coordinated collaboration across stakeholders in every field relevant to islet cell replacement.” This roadmap is a guide for moving toward our common goal of a cure for T1D as soon as possible.

Breakthrough T1D will continue to lead the way until the T1D community can choose the beta cell replacement therapy that works best for them, regardless of blood glucose management or hypoglycemia status. Everyone deserves the chance to benefit.

Sana Biotechnology’s hypoimmune (HIP) donor-derived islets are genetically engineered to avoid immune destruction without the need for immunosuppressants.

Earlier this year, we reported on an update from the first person with type 1 diabetes (T1D) to receive a transplant of these cells, which showed that they were making insulin—without immunosuppression—after four weeks. Then, at the American Diabetes Association (ADA) 85^th Scientific Sessions, we heard firsthand from Per-Ola Carlsson, M.D., Ph.D., the Principal Investigator at Uppsala University conducting the study, who provided more exciting data to a packed audience.

Now, these data have just been published in the prestigious New England Journal of Medicine in an article titled “Survival of Transplanted Allogenic Beta Cells with No Immunosuppression.”  This study was supported by the Helmsley Charitable Trust, a long-time partner of Breakthrough T1D.

Read on to learn more.

Surviving and thriving

In this first-in-human study, the recipient of Sana’s HIP islets had no detectable insulin production at the time of the transplant (as measured by C-peptide). They received a small dose of islet cells—less than the eventual therapeutic dose—implanted into the forearm to evaluate safety.

C-peptide

C-peptide is an easily measurable biomarker of insulin production and islet function.

After 12 weeks, researchers found that the transplanted islets were successfully avoiding destruction by the immune system—meaning they are surviving AND making insulin!

The recipient had decreased HbA1c levels and stable insulin production between seven days and 12 weeks post-transplant, although, as expected with the small dose of cells used in this pilot study, they still required external insulin therapy. They experienced some non-serious side effects possibly related to the surgical transplant procedure, but not the islet cells themselves. Overall, the recipient is doing well and in good health—an exciting step for the T1D community.

Why this matters

To put it plainly: this is a huge step toward cures for T1D.

Immunosuppression is a major barrier to cell therapies because of the side effects associated with them. This is the first proof-of-concept evidence that we can genetically engineer islets to avoid immune destruction—eliminating the need for chronic, broad immunosuppressants. This means that more people may have the opportunity to benefit.

Importantly, the person in this study received only a fraction of the islet cells that would eventually be used therapeutically. Researchers are just beginning to understand the full potential of engineered HIP islets. Because more islet cells means more insulin production, there’s the possibility of insulin therapy independence if higher doses of HIP islets are implanted—something that will be addressed in future studies.

Thanks to this study, we’ve gained more evidence that forearm muscles may be a possible minimally invasive site for islet transplantation. This transplant site also provides researchers with the advantage of visualizing the islets—and making sure they’re alive—using magnetic resonance imaging (MRI), which isn’t possible with the current transplant site in the hepatic portal vein.

Excitingly, Sana is working to apply this technology to manufactured islets, opening the doors to producing HIP islets at large scale. They expect to begin phase 1 clinical trials for this next-generation HIP islet therapy as early as 2026.

Cell therapies without immunosuppression are a Breakthrough T1D priority

Cell replacement therapies—especially those that do not require immunosuppression—are a priority of Breakthrough T1D’s Cell Therapies Program and the goal of our Project ACT (Accelerate Cell Therapies) initiative.

To accelerate the development of cell therapies that do not require immunosuppression, The T1D Fund: A Breakthrough T1D Venture invested in Sana to help advance their HIP technology platform. Breakthrough T1D continues to support creative and promising approaches that may eliminate the need for immunosuppression with cell replacement therapies, and we are hopeful and excited about what the future may hold.

This wouldn’t have been possible without supporters like you. Thank you for all that you do to drive Breakthrough T1D’s mission, and together we celebrate each step towards a world without T1D.

ADA Recap Series

This article is the second 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 Medical Affairs.

Cell therapies were front-and-center at ADA 2025. We have some exciting clinical trial updates and new ideas for optimizing islet transplantation.

Cell therapies

Autologous cell transplantation

Autologous cells are those removed from an individual and implanted back into the same individual. These cells can be modified in a laboratory before implantation. Autologous cells are still susceptible to autoimmunity in T1D, so cell protection strategies (gene-editing, encapsulation, immune modulation, etc.) are expected to be required.

Allogenic cell transplantation

Allogenic cells are those that are derived from a source other than the recipient, such as deceased donors or precursor-derived manufactured cells. Allogenic cell transplants require immunosuppression because they stimulate an immune response. Breakthrough T1D’s Cell Therapies program is focused on allogenic cells—specifically manufactured cells—because they can be generated at large scale.

One-year updates on Vertex’s manufactured cell therapy, zimislecel

• Presenter: Michael Rickels, M.D. (University of Pennsylvania)
• Zimislecel (VX-880) is a manufactured islet therapy that requires immunosuppression, infused into a vein in the liver in people with T1D who have impaired hypoglycemic awareness and severe hypoglycemic events.
• The phase 1/2 clinical trial, which is part of the pivotal phase 1/2/3 FORWARD-101 trial, is complete. Twelve participants received a single infusion of a full dose of cells and were followed for at least one year.
• All 12 participants achieved the primary endpoint, which was elimination of severe hypoglycemic events and HbA1c levels less than 7%. 10/12 (83%) participants are insulin independent.
• All 12 participants demonstrated sustained insulin production as measured by C-peptide, reduced external insulin therapy use, and achieved greater than 70% time in range.
• There were no serious adverse events. Mild to moderate adverse events were consistent with the immunosuppression regimen, infusion procedure, and complications from T1D.
• These data were published in the New England Journal of Medicine and represent further evidence of the curative potential of manufactured islet transplantation for T1D.
• Breakthrough T1D’s support for Doug Melton, Ph.D.—whose proprietary lab-created beta cells are now being advanced by Vertex—goes back decades, both via research grants and an investment from the T1D Fund: A Breakthrough T1D Venture.

6-month update on Sana Biotechnology’s immune-evasive islets

• Presenter: Per-Ola Carlsson, M.D., Ph.D. (Uppsala University)
• Sana’s donor-derived islet therapy engineered with Hypoimmune (HIP) technology can evade the immune system without immunosuppression.
• These cells were implanted intramuscularly in a first-in-human study into a person with T1D with no measurable insulin production.
• Six months post-transplant, this person is consistently making their own insulin, as measured by C-peptide levels. Yet, they still require external insulin therapy because they received a smaller dose of cells than the dose that would be required to achieve insulin independence. They did not experience any serious side effects, so the cells and procedure are safe and well-tolerated.
• A Mixed Meal Tolerance Test (MMTT) confirmed that these cells are not only surviving but also responding to changes in blood glucose levels.
• This is a promising first step toward a functional cure for T1D that does not require immunosuppression. Sana Biotechnology is planning on applying this technology to manufactured islets.
• Sana has received support from the T1D Fund to advance their HIP technology in islets, and Breakthrough T1D continues to work closely with them.

A new transplantation site for autologous manufactured islets

• Presenter: Hongkui Deng, M.D. (Peking University)
• Cells derived from adipose tissue (fat) can be removed from a person and chemically induced in the laboratory to become islet cells.
• Implantation of autologous manufactured islets into the sub-anterior rectus sheath in preclinical models of T1D improves glycemic control.
• In humans, this implantation site is easily accessible by an ultrasound-guided needle.
• In a first-in-human study, autologous manufactured islets were implanted into this site in a person with T1D. This person no longer needs external insulin therapy and has greatly improved blood glucose control. This person had also received a liver transplant and was taking immunosuppressants.

A new encapsulation device for immune protection of transplanted islets

• Presenter: Nicolas Laurent, Ph.D. (Adocia)
• Adoshell® is a novel islet cell encapsulation device that can shield islets from the immune system, meaning that immunosuppressants are not needed.
• The hydrogel-based device is non-degradable, easily retrievable, and allows the exchange of glucose and insulin from the vasculature surrounding the device while excluding immune cells from encapsulated islets based on pore size.
• This device showed promise in animal models, and human clinical testing is next.

Disease-modifying therapies

A major focus at ADA 2025 was addressing the underlying immune mechanisms of T1D—including alterations in immune cells that facilitate beta cell destruction and other factors that contribute to autoimmunity onset. Read on for some highlights.

The role of B cells in T1D autoimmunity

• Presenter: Mia Smith, Ph.D., DVM (University of Colorado)
• B cells are a type of immune cell that can activate destructive immune cells that facilitate autoimmunity in T1D.
• B cells can become wrongly activated against insulin-producing beta cells due to converging dysregulation of factors that regulate immunity.
• These cells represent another potential target for disease-modifying therapies in T1D.

Early detection

A key focus at ADA 2025 was the growing recognition of the heterogeneity of T1D, including autoantibody-negative disease onset, genetic variation, and the frequent misdiagnosis of T1D in adults, underscoring the need for greater diversity and inclusion in research and care. The expanded role of continuous glucose monitoring (CGM) and continuous ketone monitoring (CKM) was also highlighted, not only for daily management but as essential tools for understanding disease progression.

Using genetics to predict T1D risk

• Presenters: Richard Oram, M.D., Ph.D. (University of Exeter), Leslie Lange, Ph.D. (University of Colorado), Aaron Deutsch, M.D. (Massachusetts General Hospital), Josep Mercader, Ph.D.(Massachusetts General Hospital) and Eimear Kenny, Ph.D. (Icahn School of Medicine at Mount Sinai)
• Polygenic risk scores (PRS) estimate the risk a person has for developing a disease like T1D based on variations in different genes.
• Ancestry is a major influence on PRS, particularly based on differences in genes that regulate whether the immune system can distinguish between “self” and “non-self.”
• Most PRS models have been developed using data from European populations and have a limited ability to accurately determine risk in other ethnic groups, such as individuals of African and East Asian descent.  
• Potential applications of PRS include incorporation into screening to better understand T1D risk, ensure accuracy in diagnostic tests, and develop precision medicine-based therapeutic approaches.

Understanding how genetic diversity contributes to T1D

• Presenters: Suna Onengut-Gumuscu, Ph.D. (University of Virginia), Dominika A. Michalek, MS (University of Virginia), Aaron Deutsch, M.D. (Massachusetts General Hospital), and Stephen I Stone, M.D. (Washington University School of Medicine), among others.
• These talks highlighted several studies conducted in diverse populations to better understand the pathophysiology of T1D.
• Work presented from Consortia, such as RADIANT, focused on rare and atypical forms of diabetes.

Controversies in CGM and benefits for early detection

• Presenters: Peter Calhoun, Ph.D. (Jaeb Center for Health Research), Michael Kohn, M.D., MPP (University of California San Francisco), Nicole Ehrhardt, M.D. (University of Washington) and Tadej Battelino, M.D., Ph.D. (University of Ljubljana)
• CGM use holds value in identifying progression in early stages of T1D prior to symptomatic onset.
• There was a call to update the clinical guidelines so that the benefits of CGM can be maximized within the T1D community—including at early and later stages of T1D.
• Integrating newer measures of blood glucose, like the glucose management indicator (GMI) and time in tight range (TITR), will be essential.

Contributions of CKM to early detection

• 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).
• It will be critical to explore whether ketone monitoring could help reduce the incidence of diabetic ketoacidosis (DKA) at stage 3 clinical T1D onset.
• Early detection of rising ketones will be important for people with T1D to take action before DKA occurs.

Look out for tomorrow’s article for an update on Medical Affairs presented at ADA 2025!

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.

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.

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.

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.

Look out for tomorrow’s article for an update on Cures research presented at ADA 2025!

Clinical trials are scientific studies that tell us if a new therapy or device works in humans and is safe. All new medical products must go through this process. Clinical trials are a necessary part of getting promising treatments from the lab and into clinics, so people can benefit—including those with type 1 diabetes (T1D).

The caveat: clinical trials don’t always work as expected for everyone. People with T1D might get the placebo instead of the actual treatment. Or, they might get the treatment, but it may not be effective for them. While this can be disappointing, it’s important to remember that clinical trials are an essential part of the process for arriving at new, effective therapies—and we can learn from them at every step of the way.

This Clinical Trials Awareness Day, we’re debunking some myths and misconceptions about clinical trials. What do researchers do when they don’t work? Why are placebos necessary? Why do they take so long?

Read on to find out.

When clinical trials “don’t work”

Assumption

A negative clinical trial—one that doesn't meet its primary endpoint or that yields inconclusive data—is a waste of time and money.

Reality

All data is good data, and we can learn lessons from clinical trials to design better studies that give us more information.

Clinical trials don’t always work the way researchers hope they will. For example, in T1D, a new therapy may not lower blood glucose, or it may increase the risk of severe hypoglycemic events. If the data from the trial isn’t positive, was it all a waste of time?

The answer is: absolutely not! The scientific method involves conducting an experiment or trial, analyzing the data, and using that data to figure out the next steps. Sometimes, researchers conclude that a drug might work better for a different indication. Other times, the trial design needs to be adjusted to make sure the right outcomes are being measured or the risk for serious side effects is reduced. Scientists and clinicians essentially use “negative” trial data to rule out what doesn’t work and craft a more informed plan going forward.

“The value of a clinical trial goes far beyond whether the drug ‘works.’ We can learn critical information from mechanistic studies that allow us to fine-tune our approaches, implement personalized and precision medicine, and ultimately improve outcomes for everyone living with T1D,” explained Joshua Vieth, Ph.D., Senior Director of Research at Breakthrough T1D. Here are some case studies that help explain this idea.

The low-down on placebos

Assumption

It’s not fair for people with T1D to get a placebo instead of the study drug since it doesn’t do anything.

Reality

Placebos are required to know if a new therapy is working, and by participating in clinical trials you will receive top-tier care and contribute to medical breakthroughs that could help the entire T1D community.

Placebos are a necessary part of ethical, scientifically rigorous clinical trial design. Without them, researchers wouldn’t be able to tell if a new therapy has a clinically meaningful effect or not.

An important aspect of placebo-controlled trials is “blinding” participants, and usually clinicians, from knowing if they are giving or receiving the study drug or a placebo. This accounts for the placebo effect, which occurs when a person feels better, even though they received a placebo, because they believe that it’s having an effect. By separating the placebo effect from the actual biological effects of a new therapy, researchers can draw stronger conclusions about whether it will have a clinical benefit.

Clinical trials, especially at earlier stages, are also designed to test safety. A phase 1 trial is usually the first time that a new therapy is being put into humans. Without a placebo group, researchers wouldn’t have a clear picture of any side effects that a new treatment may have—which is critical for advancing to the next trial phases.

Clinical trials must be designed ethically: prioritizing safety, transparency, and clinical value. Placebos are a part of this, and they shouldn’t be a deterrent to enrolling in trials. People in the placebo group get state-of-the-art clinical care and are contributing to the body of knowledge that helps researchers and regulators make the right decisions about new therapies—which at the end of the day, benefits the entire T1D community.

The waiting game

Assumption

Clinical trials take too long and as such are not worth supporting.

Reality

Clinical trials take a long time because they thoroughly evaluate if a new therapy is safe and has a clinical effect before being available to everyone.

Clinical trials require coordination between lots of people: identifying study sites, making sure the clinics have the right personnel to administer a new treatment, making enough high-quality drug to conduct trials, and recruiting eligible participants. This also includes communication with regulatory agencies and extensive paperwork, data review and analysis by scientists and clinicians, writing up and publishing results, and ethics reviews.

It’s true: clinical trials take a long time. But, it’s all in the name of prioritizing people’s health, and most would agree that getting a new therapy that hasn’t been fully vetted wouldn’t be the best idea. Often, recruiting enough people is a major barrier to the advancement of trials. While many members of the T1D community participate in clinical trials, we need more people to accelerate the pace.

Conclusion: Clinical trials are thoughtfully designed—and essential to our health

Reality

Without clinical trials, we wouldn’t have access to the life-changing therapies that are available today.

Money, time, and energy spent on clinical trials is well worth the investment.  Clinical trials, in essence, are the scientific process of making sure that a new therapy is safe and effective before it gets to people with T1D. Researchers learn from unexpected results to better decide on next steps, and each aspect of trial design is well thought out and has a specific purpose. While they often take many years, in the end it’s worth it.

In short: trust the process!

“Taking part in a clinical trial is such an important contribution to the T1D field. Beyond determining whether the treatment works, we are learning critical information about how the cells of the body respond. This opens the door for next generation approaches and allows us to take a giant step forward in the development of treatments and cures. Your participation in a trial provides long-term benefits to all those currently living with, or at risk of developing T1D.”

Joshua Vieth, Ph.D., Senior Director of Research at Breakthrough T1D

Project ACT series

This article is part of a series exploring the different ways that Breakthrough T1D’s Project ACT (Accelerate Cell Therapies) is shaping the future of cell therapies for type 1 diabetes (T1D). The next article in the series will focus on Project ACT’s advocacy efforts to ensure there is a regulatory pathway to approval for these therapies and that they will be covered by payers.

Read last month’s article about challenges and solutions of T1D cell therapies.

Despite significant advances in treatments for T1D, our community still has significant unmet needs. Breakthrough T1D believes that novel cell therapies will transform T1D management, and Project ACT is how we’re going to make them a reality.

First-generation cell therapies, including FDA-approved, donor-derived Lantidra® and Vertex’s manufactured islet therapy in phase 1/2/3 clinical trials, VX-880 (Zimislecel), are incredibly promising. They have some limitations, including:

• There are not enough donor-derived islets to meet the needs of everyone with T1D.
• These therapies are only available to people with severe hypoglycemia unawareness and hypoglycemic events.
• The number of people who can receive these therapies is further limited in that they must be able to tolerate chronic, broad immunosuppression.

Current research efforts at the preclinical, clinical, and manufacturing levels are working to address these challenges. The ultimate goal is a future in which manufactured islet therapies exist in large supply, survive and produce insulin in the body after implantation, and remain protected from the immune system. Learn more about Breakthrough T1D’s Cell Therapies Program and take a closer look at what researchers are doing to turn these ideas into a reality.

Clinical trials to keep an eye on

Up-and-coming cell therapies for T1D are in the clinical pipeline and working their way towards the market, including many that Breakthrough T1D has contributed to. There are some highly anticipated (and currently enrolling!) trials that we have our eyes on right now, and we hope to see data soon. Read about each study in detail below or scroll down to see a summary table.

Recruiting cell therapies clinical trials

Where do we go from here?

The emergence of cell therapies for T1D in clinical trials is incredibly exciting for the T1D community. Advancements using deceased donor-derived islets are paving regulatory pathways for manufactured islet therapies—which are curing people with T1D in clinical trials—to make their way towards the market.

“One of the greatest effects that manufactured islet cell therapies will have for the T1D community is being able to think about their type 1 diabetes less,” explained Nicholas Mamrak, Ph.D., a scientist at Breakthrough T1D. This may soon be a reality for a subset of people with T1D as we drive towards the approval of a first-generation manufactured islet replacement therapy, reducing the day-to-day burden of managing blood glucose and insulin dosing.

The ultimate goal is to make sure manufactured islet therapies are available to everyone with T1D—ideally without the need for immunosuppression. This is the objective of Breakthrough T1D’s Project ACT.

Before cell therapies can become available for everyone, they must first receive regulatory approval. A key part of Project ACT is streamlining and advancing regulatory pathways for the treatment of T1D. To help achieve this, Advocacy and Regulatory leadership teams at Breakthrough T1D are working on a new publication capturing how day-to-day lives have changed for people with T1D who have received cell therapies. By using personal experiences to share what benefits of cell therapies matter most to patients, we can help regulators understand the powerful impact that islet replacement therapies can have.

None of this would have been possible without the T1D community’s continued generosity and support, as we all work together to move the needle forward.

Have an impact by participating in clinical trials

Without clinical trials, we would never know if new therapies developed by scientists in the lab could make a difference in people’s lives. This is where the T1D community comes in—by volunteering to participate in clinical trials, you become uniquely positioned to help drive biomedical research forward. Moreover, by participating, you help not only yourself, but everyone with T1D. Find a clinical trial near you and see if you are eligible to participate. Connect with a Clinical Trial Education Volunteer in your area, who can answer any questions you may have.

They’re all over the news: Ozempic ®. Trulicity ®. Jardiance ®. Mounjaro ™. And more.

These drugs are all approved for glucose control in type 2 diabetes (T2D). Some of them also have additional indications reflecting their demonstrated benefits for cardiovascular disease, kidney health, and obesity.

None of these drugs are currently approved for people with type 1 diabetes (T1D). However, a recent consensus report addressed the growing interest in GLP-1 receptor agonists as an adjunctive therapy for T1D and their “potential to improve glycemic and metabolic outcomes without increasing the risk of severe hypoglycemia or diabetic ketoacidosis.”

Let’s examine GLP-1 therapies and SGLT inhibitors and consider how drugs like Ozempic may one day help people with type 1 diabetes.

GLP-1 therapies

GLP-1 (glucagon-like peptide-1) receptor agonists work in multiple ways to control blood glucose and obesity. They block the release of glucagon, stimulate insulin production, slow the rate at which your stomach empties, and increase the sensation of feeling full. They are usually injected, but oral versions are available.

In people with T2D, this class of drugs lowers blood sugar levels and, for most people, causes weight loss. GLP-1 therapies have also been shown to reduce the risk of long-term cardiovascular complications often experienced by people with T2D, such as heart attack and stroke.

GLP-1 drugs include Ozempic/Rybelsus/Wegovy (semaglutide), Trulicity (dulaglutide), Victoza (liraglutide), and Mounjaro (tirzepatide), among others.

When GLP-1 treatments hit the market in the early 2000s, Breakthrough T1D and others funded several clinical trials to test whether GLP-1 receptor agonists, in addition to insulin, improved outcomes for people with type 1 diabetes. While some of these studies showed that the addition of GLP-1 therapies to insulin led to improvements in HbA1c, total insulin dose, and weight, the benefits were relatively modest and accompanied by some side effects like hypoglycemia. As a result, these studies did not lead to GLP-1 receptor agonists being highly adopted for use by people with T1D.

However, these trials were done with older GLP-1 drugs. We are investigating whether the newest, most advanced GLP-1 therapies (like Ozempic) will improve the health of people living with type 1 diabetes. (See below!)

SGLT inhibitors

SGLT (sodium-glucose co-transporter) inhibitors are oral medications for people with T2D that lower blood sugar by preventing the kidneys from reabsorbing glucose, leading to the excretion of sugar through the urine.

In addition to improving blood sugar for people with and without T2D, these drugs also provide benefits such as weight loss, blood pressure reduction, and transformative benefits to the heart and kidneys.

SGLT drugs include Jardiance (empagliflozin), Farxiga (dapagliflozin), and Invokana (canagliflozin), among others. Despite demonstrating improved glucose control for people with type 1 diabetes, SGLTs have not been approved for people with T1D in the U.S. Increased risk of diabetic ketoacidosis (DKA) in this population limits the use of these therapies. A key Breakthrough T1D priority is to find ways to mitigate this risk so people with T1D can also take advantage of the SGLT cardiovascular and renal benefits.

Breakthrough T1D-funded research in GLP-1 and SGLT therapies

Breakthrough T1D has a long history with GLP-1 medications like Ozempic. In the 1980s, Breakthrough T1D-funded researcher Pauline Kay Lund, Ph.D., was the first to clone the hormone glucagon and discover two new hormones, one of which was GLP-1.

Today, there is real-world evidence of GLP-1 receptor agonists improving the lives of people with type 1 diabetes.

Evidence demonstrates that semaglutide (Ozempic) or tirzepatide (Mounjaro) have the potential to lower A1c, increase time-in-range, and reduce the amount of daily insulin needed in people with T1D. More research is needed in this area. That’s where Breakthrough T1D comes in!

Breakthrough T1D-funded research on GLP-1 and SGLT therapies is investigating the benefits of these drugs for people with T1D, including reducing the risk of common complications of type 1 diabetes like cardiovascular disease and kidney disease.

Snapshot of active clinical trials in GLP-1 and SGLT therapies

Here are a few examples of Breakthrough T1D-funded clinical trials in GLP-1 and SGLT therapies that are currently underway:

Our commitment to improving lives

Breakthrough T1D strives to improve health outcomes in people living with type 1 diabetes. Insulin therapy alone is often not enough for people with T1D to achieve glucose and metabolic control. The use of adjunctive drugs that complement insulin therapy can help. Since the FDA has already approved these medications for treating other conditions, positive results from these clinical trials could speed up the adaptation of these therapies for people living with T1D.

Learn more about clinical trials and how they are advancing breakthroughs for the T1D community.

The unexpected diagnosis

Katie Howell, a Mississippian-turned-New Yorker, has a wide array of hobbies: crafting pottery at her local ceramics studio, enjoying old movies in the theater, cozying up with a book in Prospect Park, and taking in the sun at Rockaway Beach. Katie moved to Brooklyn after completing a Master of Public Administration degree at the University of Tennessee, Chattanooga, and she’s thoroughly enjoying getting to know her new neighborhood.

Suddenly, things took a turn. Last year, Katie started experiencing symptoms of something unknown—for three months, she had no idea what was going on with her body. Then, in a moment of complete shock, 25-year-old Katie was diagnosed with type 1 diabetes (T1D). “Without a family history of T1D and without any health issues of my own, being diagnosed with a sudden, serious chronic illness could not have been more unexpected,” Katie explained.

At the time of her diagnosis, Katie was confronted with a flood of emotions. There was not a single person in her life that had T1D or could understand her experience. “…one of the most challenging parts of being diagnosed with a chronic illness is accepting it […]. This comes with a lot of hopeless feelings, and it is tough to surrender control to an incurable, pervasive, and expensive health condition,” Katie lamented.

Feeling alone and lost, she had no choice but to accept that she was dealing with a major life change—whatever that meant for the future.

Influenced

It wasn’t long before Katie took to social media to learn more about her diagnosis and connect with the T1D community. On Instagram, she stumbled upon Lauren Bongiorno, a T1D influencer. Ms. Bongiorno posted a video promoting DIAGNODE-3, a phase 3 clinical trial for the disease-modifying therapy Diamyd® for early-stage T1D.

Katie found that DIAGNODE-3 was enrolling at The Pediatric Diabetes Center at Hassenfeld Children’s Hospital at NYU Langone. After reaching out to the team at NYU, she realized that the stars had aligned: they had just opened enrollment, and after completing the necessary screening, Katie would be Participant Number One.

“It gets easier every visit!”

Katie received her first study injection in January and will get her third and final injection this month, followed by routine check-ins. This includes blood work, physical exams, and mixed-meal tolerance tests to measure her body’s ability to produce insulin.

As per the study protocol, Katie doesn’t know if she’s receiving the placebo or the study drug, Diamyd®. Still, she likes being in the study: she’s made meaningful connections with the trial team, has learned a lot about T1D, and feels that she’s making a difference—not just for herself, but also for biomedical research.

Katie’s biggest hurdles? Bloodwork and hospitals. “One challenge of this study is the routine blood work and being treated at the hospital. However, it does feel like exposure therapy. It gets easier every visit!” she exclaimed.

Finding her community

Since her diagnosis, Katie has made lasting relationships with others in the T1D community. She connected with the Greater New York Metro Chapter of Breakthrough T1D after volunteering at a Walk in NYC last fall. They introduced her to a group chat with other newly diagnosed young women, where they can ask questions, network, and learn from each other as they navigate their new realities.

“My advice to someone considering [the DIAGNODE-3] trial would be that, though the study is a commitment and an undertaking, they are taking part in discovering medical breakthroughs and T1D treatment research.”

Katie Howell

Participate in clinical trials

Clinical trials are key to bringing medical advancements from the lab to the clinic. This wouldn’t be possible without brave people with T1D, like Katie, who volunteer to participate. These studies offer the potential for life-changing treatment and move the ball forward for the T1D community.

Use our Clinical Trials Matching Tool to find a trial near you. Connect with a Clinical Trial Education Volunteer in your area to learn more about trial participation and answer any questions you may have.

Disease-modifying therapies

Also "DMTs" for short, these therapies prevent, slow, halt, or reverse T1D progression.

With the establishment of our Medical Affairs team, we are reaffirming our organization’s commitment to creating a world where every individual with type 1 diabetes has access to life-changing therapies. By addressing systemic barriers and fostering clinical readiness, Breakthrough T1D will be pivotal in driving the timely adoption of emerging therapies and transforming care.” 

Thomas Danne, M.D.

Breakthrough T1D Chief Medical Officer, International

Our goal is to make this education as accessible as possible.”

Julianne Lally, DMSc, MHS, PA-C

Breakthrough T1D Associate Director of Community Screening and Clinical Trial Education

Detecting T1D before symptoms present

A simple blood test can detect T1D in the earlier stages—before obvious symptoms develop. The biggest challenge is educating clinicians and the general population about it.  

“Endocrinologists, Pediatricians, and some other specialty physicians learn about T1D screening and monitoring during their residencies, but it’s not a part of the general curriculum of the first four years of medical school,” said Lally, who built the learning management system for the new resources and is organizing the virtual offerings. “We’re working to advance that knowledge to yes, doctors, but also other clinicians whose patients could benefit.”

Many clinicians hesitate to order unfamiliar tests—especially if they are unsure what to do with the results. Most people who see any kind of healthcare provider could benefit from screening for T1D—according to a paper published in the journal US Endocrinology, roughly 85 percent of people diagnosed with type 1 do not have a blood relative with the autoimmune disease. 

“Clinicians need to learn about the stages of type 1 and the specific autoantibody tests that identify type 1 versus type 2 and identifying type 1 in individuals at risk before they need insulin,” said Colleen Buggs-Saxton, M.D. Ph.D.

Buggs-Saxton, a Pediatric Endocrinologist at Wayne Pediatrics in Michigan, is the clinical leader of a Breakthrough T1D Early Detection pilot clinic. Using the new resources, she and Albanese-O’Neill are going to lead a grand rounds about T1D early detection at her institution, which is affiliated with the Wayne State University School of Medicine and healthcare system. 

Clinicians should consider autoantibody testing for adults who have been diagnosed with type 2 but don’t have typical clinical features and require insulin to manage their blood sugars.” 

Colleen Buggs-Saxton, M.D., Ph.D.

Pediatric Endocrinologist

Grand rounds

Grand rounds are educational meetings and presentations for clinical teams at a given institution or healthcare facility to provide a summary of updates to the standards of care.

I think of research, advocacy, and medical affairs as three legs of a stool—in terms of clinical adoption, each helps answer a different question. Research: Does it work? Advocacy: Will the regulators approve it and will insurance companies cover it? Medical Affairs: Do clinical teams have the competency and readiness to prescribe the treatment and educate and support people with T1D?” 

Anastasia Albanese-O'Neill, Ph.D., APRN, CDCES

Breakthrough T1D Associate Vice President of Community Screening and Clinical Trial Education

The most challenging part is helping patients understand what a clinical trial is, what it involves, and how previous scientific advances were only possible because of clinical trials. Healthcare providers often don’t have enough time in their busy clinics to discuss this with patients and families.”

Laura Jacobsen, M.D.

Pediatric Endocrinologist

Cell Therapies

Also called islet cell therapies, these therapies replace destroyed beta cells so that people with T1D can again produce their own insulin.

Marjorie Lazarre (R) with her daughter, Ava (L)

A life-changing event at age 14 determined Marjorie Lazarre’s career.

“My sister was diagnosed with type 1 diabetes (T1D) after being rushed to the hospital,” she recalled. “I decided to go into pharmacy as a way to better understand medication and educate myself to support her, as well as other patients.”

Marjorie received her doctoral degree in pharmacy from Howard University in Washington, D.C., and completed a pharmacy practice residency at Yale New Haven Hospital. She currently serves as the Director of Pharmaceutical Procurement and Business Practices at Yale New Haven Hospital.

Another life-changing event

Several years ago, Marjorie and her husband received devastating news: their 7-year-old daughter, Ava, had type 1 diabetes. “Again, my life changed,” she said. She started looking for ways to help improve her daughter’s life beyond the medical field. “I wanted to dedicate my effort not only to understanding medication but supporting the advocacy and philanthropy efforts of Breakthrough T1D.”

Marjorie joined her Breakthrough T1D Community Board, and her family became a top fundraising team for their local Walk. They also helped with support groups and community outreach events. Still, they wanted to do more.

Clinical trials: A path to cures

Marjorie saw firsthand the “tremendous shift from cumbersome needles and finger sticks” to continuous glucose monitors (CGMs) and insulin pumps. She knows none of these advancements would have been possible without clinical trials. So, her family started taking part in a variety of type 1 diabetes clinical trials, ranging from simple surveys to mental health analysis to blood tests.

She then became a Breakthrough T1D Clinical Trial Education Volunteer, helping families find clinical trials that are a good fit and increasing participation to fuel research for T1D. “Clinical trials are the only way to get to a cure,” she said. “The more folks that participate, the more data we have to improve and optimize treatment options.”

Marjorie is hopeful that her next life-changing event will be a cure for T1D. “I see continued improvement to the quality of life through devices and medicines,” she said. “To find a cure for type one diabetes would change so many lives.”