New Disease-Modifying Therapies that Delay T1D Onset

While many DMTs, such as immunotherapies and beta-cell regeneration, may yield better results in individuals with some remaining beta-cell function, staying informed is key. These emerging treatments can potentially change the lives of people with type 1 diabetes (T1D).

As more individuals develop T1D at various ages (from two months to golden agers in their 70s and 80s), the unmet need for therapies that address the disease at its root, rather than manage its symptoms, is becoming increasingly vital to the T1D community.

The Goal of Disease-Modifying Therapies

Disease-modifying therapies treat the underlying autoimmune destruction of beta cells.

Essentially, they have the capacity to:

1. Stop the immune system from attacking the insulin-producing cells
2. Spur on healthy beta cell growth
3. Protect the existing functioning beta cells

Disease Modifying Therapies for T1D

Most importantly, since type 1 diabetes has three stages, the benefits for those in the early stages (1 or 2) can potentially be huge, as they protect pancreatic beta-cells and their function.

Here are the stages broken down:

Stage 1

Two or more diabetes-related autoantibodies appear in the blood, suggesting that the immune system is attacking the insulin-producing beta cells in the pancreas. Blood glucose levels are still normal, and symptoms have not appeared.

Stage 2

Beta cell destruction begins, leading to abnormal blood sugar levels, but still no overt symptoms.

Stage 3

Insulin dependence begins with a full-blown autoimmune attack on the insulin-producing beta cells. The most common T1D symptoms are frequent urination, excessive thirst and hunger, unexplained weight loss, blurry vision, and extreme fatigue.

Prevention and Early Detection

Also, as early T1D detection gains traction, not only for the life-saving benefits, i.e., safe-guarding individuals from diabetic ketoacidosis (DKA), a dangerous complication of undiagnosed diabetes, but especially for the disease-modifying therapies (DMTs) that can delay the onset of type 1 for close to three years.

The Many Benefits of DMTs

While many DMTs are still in the early stages of clinical trials, they offer hope to build on for slowing or reversing T1D’s progression. Here’s what else they may do:

1. Potential for Improved Glycemic Control

DMTs may help retain or regenerate beta-cell function, enabling natural insulin. Even a small amount of preserved insulin production can improve glucose control, reduce variability, and lower insulin requirements.

2. They May Reduce the Risks of Long-Term Complications

When blood sugar is high for too long, T1D complications may arise, including heart disease, nerve damage and vision loss. As DMTs can slow the disease’s progression, they may help remove these risks.

3. DMTs May Lessen Hypoglycemia and Severe Highs

As DMTs sustain beta-cell function, they can reduce the chances of DKA and hypoglycemic episodes, keeping blood sugar more stable.

4. Delay the Need for Insulin

Despite the recent government claim that insulin is capped, insulin therapy remains costly for many individuals. Besides the numerous health benefits to the body, preserving beta cell function and insulin secretion is smart financially.

5. Potential for an Evolving Functional Cure

As these therapies work to delay or halt the disease’s progression, they offer future alternatives to diabetes management than simply treating the symptoms.

6. Participation in Clinical Trials and Current Research

As many DMTs undergo preclinical and clinical stages to prevent or delay the onset of T1D, ongoing research holds promise for all individuals with diabetes.

Move over, Tzield; here are some competing DMTs in the pipeline!

Disease Modifying Therapies for T1D

Immunotherapies that target the autoimmune attack have gotten a bad rap in the past due to the fact they suppress the immune system, which can lead to dangerous side effects and exposure to diseases like cancer.

However, the therapies below work by modifying the immune system to protect the existing beta cells—and they’re getting better, reducing adverse effects.

Teplizumab (Tzield)

Sanofi’s Teplizumab, sold under the brand name Tzield, is a treatment that helps prevent the progression of T1D. It’s the first FDA-approved DMT to delay the onset of type 1 diabetes.

Tzield is an anti-CD3 monoclonal antibody that binds to CD3 on T cells (part of the immune system). T cells, a type of white blood cell called lymphocytes, help protect the body from infection. 

Tzield is typically given as a daily infusion for 12 days. It’s approved for patients eight years or older with preclinical stage 2 T1D and has been shown to delay the onset of T1D for nearly three years! Additionally, Tzield’s PROTECT trial works with established type 1s in stage 3.

Verapamil

The medication, verapamil, used to treat high blood pressure, has demonstrated beta cell preservation in individuals with type 1 diabetes. A National Institutes of Health (NIH) study reported that verapamil might improve diabetes control in type 1 diabetes patients. Verapamil partially preserved c-peptide secretion at 52 weeks for newly diagnosed children and adolescents.

Breakthrough T1D (formerly JDRF) has supported verapamil research for over twenty years and is funding clinical trials used with other DMTs like Tzield. 

This NorCal teen, Brody Paine, was diagnosed with T1D, and his family immediately enrolled him in a Breakthrough T1D-funded clinical trial at Stanford University to extend his honeymoon phase. Read more about Brody's story and other clinical trials at jdrf.org/norcal/blog.

Abatacept (Orencia)

Many disease-modifying therapies are crossover drugs that treat other autoimmune conditions. Abatacept, a drug used to treat rheumatoid arthritis, has shown promise in slowing beta cell destruction and preserving insulin secretion. It works by blocking T-cell activation and may slow down beta cell loss.

TrialNet’s new T1D RELAY study tests abatacept in combination with rituximab-pvvr in newly diagnosed T1D patients.

Rituximab

Close on Tzield’s heels is another monoclonal antibody, Rituximab, that targets B cells. This B-cell-depleting therapy has been studied for its role in modulating autoimmunity in T1D.

Researchers are studying this B-cell depleting therapy as a potential treatment for type 1 diabetes because it depletes B cells (a type of immune cell), which also destroy the insulin-producing beta cells.

After Rituximab reduces B cells, it binds to the CD20 protein, limiting the autoimmune attack and slowing down the decline of beta cell function. Rituximab is currently in several clinical trials, including a TrialNet study, which combines another immune therapy, abatacept. This study is currently enrolling participants.

Golimumab (TNF Inhibitors)

Golimumab, another promising monoclonal antibody, works as a TNF-alpha blocker to preserve beta-cell function. One New England Journal of Medicine study showed that newly diagnosed children and adolescents with T1D responded well by producing more insulin than the placebo test group.

Other Therapies that target B cells and T cells

Phaim DMX4001

The biotech company Phaim Pharma uses an Antigenic Immune Modulation (AIM) platform to develop treatments for autoimmune diseases like T1D. Phaim’s immunomodulator, DMX4001, completed a preclinical animal study demonstrating normalized blood glucose and improved T cell function.

Phaim breaks up the protein related to the disease, creating a ‘unique soup of antigenic epitopes’ formulated into the drug.” Phaim’s goal is to break reliance on immunosuppressant drugs, which can lead to dangerous side effects.

T1DM Triple Therapy by Levicure

The pharma start-up Levicure has developed a “triple therapy” (GABA, a DPP-4i, and a PPI) to treat T1D by attempting to restore insulin-secretory function in recent type 1 patients. Levicure’s therapy aims to induce remission through beta cell regeneration. Its combination therapy consists of two FDA-approved drugs and a proprietary extended-release gastro-retentive formulation of GABA.

A recent clinical study in T1D patients and animal models showed that the drug could accelerate the remission of T1D by restoring insulin production. Levicure’s T1DM human study involved 19 patients. One group of 10 had early-onset T1D, and after 26 weeks, they reduced their insulin demands by 69% and increased their c-peptide by 147%. Another group of nine patients reduced their insulin demands by 38%.

Diamyd

Diamyd’s immunotherapy focuses on preserving beta cells and improving glycemic control in type 1 diabetes. The medication halts the immune system’s attack by reprogramming it to ignore GAD, the protein that can trigger the autoantibodies that damage the pancreas’ beta cells.

Read more on Diamyd’s clinical trial for newly diagnosed T1Ds.

Type 1 Clinical Trials using DMTs

If you’re interested in accessing clinical trials for disease-modifying therapies for (T1D), here are three ways you can get started:

1. Clinical Trial Databases

• ClinicalTrials.gov: Search for “type 1 diabetes” and filter for intervention trials or specific treatments like beta cell regeneration.
• Breakthrough T1D (formerly JDRF) Clinical Trial Finder: A user-friendly tool to match people with T1D to relevant trials.
• TrialNet: A global network focusing on preventing and slowing T1D progression.

2. Check with Major Diabetes Research Centers

• Joslin Diabetes Center (Harvard) – USA
• Benaroya Research Institute (Seattle) – USA
• Barbara Davis Center for Diabetes (Colorado) – USA
• University of Florida Diabetes Institute
• University of California, San Francisco (UCSF) Diabetes Center
• DRI (Diabetes Research Institute, Miami)

3. Contact Biotech or Pharma Companies

Companies like Vertex Pharmaceuticals (VX-880 trials), Provention Bio (Teplizumab trials), and ViaCyte (stem cell therapies) sometimes post trial details on their websites.

Make Screening a Priority

Though long-term efficacy is still questionable for most, these DMTs are moving in the right direction by preventing pancreatic beta cell destruction, preserving insulin production, reducing dangerous complications, and minimizing the need for immunosuppression — viable innovative discoveries on the path to a cure.

Disease-modifying therapies offer potential treatment in the T1D progression. Still, each research advancement brings us a step closer to a cure for all stages of the disease, which is why screening is so significant. The more individuals tested for early stages, offers a deeper pool of research for scientists.

Learn more about T1D early screening options and resources.