Insulin transformed type 1 diabetes from a fatal disease into a manageable chronic condition. A century later, researchers are asking whether cell replacement and immune tolerance can move treatment closer to durable insulin independence.
November 24, 2025
Author: YY
For people living with type 1 diabetes (T1D), daily disease management remains demanding: glucose monitoring, insulin delivery, meal planning, and constant adjustment. Since insulin was discovered in 1921, treatment technology has advanced dramatically, but insulin replacement does not restore the pancreatic beta cells destroyed by autoimmunity.
Today, several research strategies are trying to address the disease more directly. Cell replacement seeks to restore insulin-producing cells. Immune-tolerance approaches aim to stop the immune system from attacking beta-cell antigens. These strategies remain experimental for most patients, but they are beginning to define what a future 'functional cure' might require.
Two developments in 2025 illustrated the range of approaches. Novo Nordisk announced that it would close its cell-therapy research unit as part of a broader restructuring. Around the same time, EVOQ Therapeutics announced a collaboration with Sanofi worth more than $500 million in potential payments to develop antigen-specific immune-tolerance therapies using EVOQ's NanoDisc platform.
1. Why Type 1 Diabetes Still Requires Lifelong Treatment
Type 1 diabetes is an autoimmune disease in which the immune system attacks pancreatic beta cells, progressively reducing or eliminating endogenous insulin production. Genetic susceptibility—particularly specific HLA backgrounds—interacts with environmental factors, and once clinically established the disease generally requires lifelong insulin replacement.
Insulin therapy has evolved from animal-derived preparations to recombinant human insulin, rapid-acting and long-acting analogs, pumps, continuous glucose monitors, and hybrid closed-loop systems. These systems can automate part of insulin delivery and improve time in range, but they remain forms of physiologic replacement rather than repair of the underlying autoimmune process.
Adjunctive therapies such as GLP-1 receptor agonists and SGLT2 inhibitors have been studied in selected people with T1D, but they are not substitutes for insulin and are not standard first-line disease-modifying treatments. The clinical objective remains safe glucose control while preventing hypoglycemia, ketoacidosis, and long-term complications.
This is why the idea of a cure is difficult to define. A meaningful cure would need to restore sufficient endogenous insulin function, protect that function from recurrent autoimmunity, and do so with a safety, manufacturing, and access profile that is realistic for a chronic disease.
2. Type 1 Diabetes Cell Therapy: Replacing Lost Beta-Cell Function
Why Novo Nordisk stepped back from cell therapy
In October 2025, Novo Nordisk announced the closure of its cell-therapy research and development unit as part of a broader corporate restructuring. Reuters reported that nearly all of the approximately 250 employees in the unit were affected. The portfolio had included beta-cell replacement work in T1D, a Heartseed collaboration in heart failure, and cell-therapy research in Parkinson's disease.
The decision should not be read as proof that cell replacement cannot work. It reflects the strategic and industrial difficulty of the modality: long development timelines, complex manufacturing, immune rejection, and uncertain commercialization can be hard to reconcile with a large pharmaceutical company's portfolio priorities.
The scientific objective remains compelling. Pluripotent stem cells can be differentiated into insulin-producing islet-like cells, potentially creating a renewable source of replacement tissue. The difficulty is maintaining consistent cell quality at scale and protecting transplanted cells from both allogeneic rejection and the underlying autoimmune process that caused T1D in the first place.
Encapsulation and immune-protection devices can reduce direct immune exposure, but they introduce their own engineering constraints, including oxygen and nutrient transport, fibrosis, device durability, and retrieval. These issues have made beta-cell replacement as much a biomaterials and manufacturing problem as a cell-biology problem.
3. What Lantidra Proved—and What It Did Not
In 2023, the FDA approved Lantidra (donislecel), an allogeneic pancreatic islet cellular therapy for a narrowly defined group of adults with T1D who remain unable to approach target HbA1c because of recurrent severe hypoglycemia despite intensive diabetes management.
Lantidra is prepared from deceased-donor pancreatic islets and infused into the hepatic portal vein. In the two studies supporting approval, 30 participants received one to three infusions. The FDA reported that 21 participants achieved insulin independence for at least one year; 10 remained insulin independent for more than five years.
The result is important because it confirms that transplanted islet cells can restore clinically meaningful endogenous insulin production in selected patients. But the therapy also shows why islet transplantation is not yet a broadly scalable cure. Donor tissue is limited, the procedure is specialized, and recipients require immunosuppression. In the FDA review, serious adverse reactions were common and included complications related to the procedure and immunosuppressive therapy.
Lantidra is therefore best viewed as evidence that functional insulin independence is biologically possible through cell replacement, not as a routine therapy for the broader T1D population.
4. Stem Cell-Derived Islet Therapy: Building a Renewable Cell Source
Stem cell-derived islet therapy is designed to remove the donor-supply bottleneck by manufacturing insulin-producing cells from pluripotent stem cells. Vertex's zimislecel (formerly VX-880) has become one of the most closely watched programs in this area.
In 2025, Vertex reported that all 12 participants with at least one year of follow-up after a full dose of zimislecel achieved the recommended HbA1c target and time-in-range goals, and 10 of the 12 were insulin independent at Month 12. These findings provide important clinical evidence for stem cell-derived islet replacement.
However, zimislecel still requires chronic immunosuppression, so it does not solve the central immune problem. The long-term goal for the field is to combine a renewable beta-cell source with a method of protecting those cells without imposing unacceptable systemic immune suppression.
5. Immune Tolerance Therapy: Can the Immune System Be Re-Educated?
Cell replacement addresses the loss of beta cells. A different strategy is to address the immune mistake that destroys them.
In October 2025, EVOQ Therapeutics announced a collaboration and license agreement with Sanofi centered on EVOQ's synthetic HDL NanoDisc platform. EVOQ is eligible to receive more than $500 million in upfront, preclinical, development, and sales milestone payments, plus tiered royalties. Sanofi will be responsible for development and commercialization.
The platform is designed to deliver disease-relevant antigens together with immune-modulating signals to antigen-presenting cells. The goal is antigen-specific tolerance: reducing immune responses against defined self-antigens without broadly suppressing the entire immune system.
How antigen-specific tolerance differs from systemic immunosuppression
Traditional immunosuppressive medicines reduce immune activity across broad pathways. That can be clinically useful, but it can also increase infection risk and create cumulative toxicity. Antigen-specific tolerance aims for a narrower effect—teaching the immune system to tolerate a particular self-antigen while preserving protective immunity elsewhere.
EVOQ's NanoDisc approach remains preclinical for T1D. The company and its academic collaborators have reported proof-of-concept work in autoimmune models, and the Sanofi partnership reflects confidence in the platform's potential. However, claims of a durable human cure would be premature. Key questions include which antigens should be used, how much patient-to-patient variability matters, how long tolerance persists, and whether the platform can be manufactured and dosed reproducibly in humans.
6. From Replacement to Immune Reprogramming: What a Functional Cure May Require
The contrast between cell replacement and immune tolerance can make the field look like a choice between two competing strategies. In reality, a durable functional cure may require both.
A replacement-cell therapy can restore insulin production, but without immune protection the new cells may remain vulnerable. An immune-tolerance therapy can reduce autoimmune attack, but if too much beta-cell mass has already been lost, immune control alone may not restore sufficient insulin production. The most durable future strategies may therefore combine beta-cell replacement or preservation with targeted immune modulation.
This also reframes the significance of Novo Nordisk's retreat from cell therapy and Sanofi's investment in immune tolerance. They are not a simple winner-and-loser comparison. They reflect different assessments of where scientific and industrial risk should be taken.
The harder question is not only whether insulin independence can be achieved in a trial, but whether it can be delivered safely, reproducibly, affordably, and at a scale appropriate for millions of people living with T1D.
Can Type 1 Diabetes Be Cured Today?
For the general T1D population, there is currently no broadly available therapy that can be described as a cure. Insulin remains essential treatment for most patients. Lantidra can produce insulin independence in selected adults with severe recurrent hypoglycemia, but requires donor islets and immunosuppression. Stem cell-derived islets and antigen-specific immune-tolerance therapies are advancing the science, but they remain specialized or investigational approaches.
The field has nevertheless moved beyond a purely theoretical question. Clinical data now show that endogenous insulin production can be restored through cell replacement, and increasingly sophisticated immune technologies are being developed to preserve or re-establish immune tolerance. The path to a practical cure will depend on bringing those biological advances together with scalable manufacturing, long-term safety, and access.
Why This Matters
For diabetes and regenerative-medicine researchers, the definition of a cure is becoming more precise. The challenge is not simply to replace insulin, but to restore durable beta-cell function while controlling the autoimmune process that caused the disease. Cell therapy and immune tolerance address different parts of that problem, and their convergence may be more important than either approach alone.
References
• U.S. Food and Drug Administration. Lantidra (donislecel) approval and Summary Basis for Regulatory Action, 2023.
• Reuters. Novo Nordisk shuts cell therapy unit amid restructuring, October 10, 2025.
• EVOQ Therapeutics. Collaboration and License Agreement with Sanofi, October 16, 2025.
• Vertex Pharmaceuticals. Zimislecel Phase 1/2 data presented at ADA, June 20, 2025.
• Fung JJ, et al. Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes. N Engl J Med. 2025;393:858-868.
• Herold KC, et al. Replacement of Beta Cells for Type 1 Diabetes. N Engl J Med. 2025;393:917-921.
• Dang HP, et al. Cell delivery systems: Toward the next generation of cell therapies for type 1 diabetes. J Cell Mol Med. 2022;26(18):4756-4767.
Reprinted from BiG. BiG Bio Innovation Society is a nonprofit life-science industry platform connecting researchers, companies, investors, and innovators, and is an affiliated association of Direct2Lab.
