Disease-modifying therapies (DMTs) are treatments that prevent, slow, or reverse type 1 diabetes (T1D) by preserving or restoring insulin-producing beta cells. While there are several DMTs in clinical trials, there is only one that has been approved. A new Breakthrough T1D publication lays out how companies developing DMTs can incorporate strategic clinical trial design to evaluate the safety and efficacy of their products. The goal? More therapeutic options for more people—and sooner.
New Publication Alert!
The manuscript, titled “Clinical Trial Design Considerations for the Development of Disease-Modifying Therapies for Type 1 Diabetes,” was published in October 2026 in Diabetes. The authors included expert collaborators in addition to several Breakthrough T1D staff:
- Josh Vieth, Ph.D., Senior Director of Research and lead of our DMT program
- Stephen Karmpen, Pharm.D., Senior Director of Regulatory Affairs
- Esther Latres, Ph.D., Senior Vice President of Research
- Sanjoy Dutta, Ph.D., Chief Scientific Officer
Why Do We Need this Roadmap?
DMTs can preserve beta cells, helping the body make its own insulin for longer. We know that more beta cells mean better health outcomes—improved blood sugar, reduced short- and long-term complications, and easier daily management. The best insulin for your body is the insulin it makes.
Teplizumab (Tzield) is the first approved DMT for stage 2 T1D and recently diagnosed stage 3 T1D. While this is a great achievement for the T1D community, we need more options that address the underlying cause of the disease so people can have a choice and select the therapy that best fits their needs. This has been challenging because DMT clinical trials have historically relied on outdated endpoints that make them require more time, money, and participants, which have slowed their movement through the drug development pipeline.
The Challenge
Several DMTs have been shown to preserve beta cells in clinical trials, but few of these therapies have advanced to pivotal phase 3 studies, which is the final step before seeking regulatory approval.
That’s why we need this roadmap: to get more DMTs to phase 3 trials—and eventually approved.
Accelerating DMTs Through the Pipeline
The Solution
Strategic endpoints, combination strategies, and thoughtful clinical trial design can accelerate more DMTs into pivotal phase 3 clinical trials.
What is a Clinical Trial Endpoint?
A clinical trial endpoint is the specific health outcome being measured to assess if a therapy is effective. Some examples are low blood-sugar events or the rate of developing long-term complications. Surrogate endpoints are those that have proven to predict a clinical benefit, like HbA1c as a readout for the risk of long-term complications. Surrogate endpoints allow us to see the effects of a drug much faster, easier, and sometimes more clearly than other endpoints.
Thoughtful and targeted clinical trial design is key to moving DMTs through the drug development pipeline quickly and safely. Researchers and regulators need to carefully consider:
Matching the mechanism with the population
Different DMTs may have distinct effects on the immune system depending on the T1D stage and each person’s genetic background or immune profile.
Combining therapies to maximize efficacy
Combining more than one DMT, especially those with different mechanisms of action, may have a greater effect compared to either used alone. For example, in the WAVE T1D clinical trial, verapamil (a drug that can reduce beta cell stress) is being tested together with ATG (which targets the immune cells responsible for destroying beta cells).
Repurposing approved therapies in other autoimmune diseases
For therapies that are already approved, we may be able to leverage existing knowledge about their safety and dosage without having to complete duplicative studies in T1D. One example is baricitinib, a JAK inhibitor that is already approved for rheumatoid arthritis, alopecia, and more. It’s currently in two Breakthrough T1D-funded phase 3 clinical trials to see if it can delay early-stage T1D progression or preserve beta cells shortly after diagnosis.
Incorporating more efficient endpoints
Endpoints that can be measured earlier will help DMT clinical trials move faster. Breakthrough T1D has been advocating for C-peptide, a marker of beta cell function, to be accepted by the FDA as a validated surrogate endpoint to speed clinical trials and support full approval of DMTs.
Centering on the lived T1D experience
Ensuring the participants’ voices are heard during clinical trials is key to developing DMTs that meet the needs of the T1D population.
10
The number of DMTs that have preserved or slowed the decline of beta cell function after diagnosis in clinical studies, as measured by C-peptide.
You read that right: we have clinical evidence that 10 DMTs can help the body make its own insulin for longer, and there are several others in early-phase trials that have shown promise in preclinical studies. To move these therapies to phase 3 studies, researchers and regulators need to work together so that clinical trials are designed and executed with the T1D community in mind.
Key Takeaways
- DMTs can preserve the body’s own insulin production, which is associated with better health outcomes.
- People with T1D need more options that address the underlying cause of the disease.
- Based on data from clinical trials, we know of several DMTs that show promise in T1D, but few have made it to phase 3 studies.
- Thoughtful clinical trial design, centered around mechanisms, target populations, combination approaches, repurposing of approved therapies, better endpoints, and the lived T1D experience, is the key to accelerating DMTs through the pipeline.
