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type1.science

End goal 02 — a cure

Road to a cure

From injected insulin to restoring the body's own insulin production — found early, protected, and durable.

This roadmap is the site’s spine: where we are today, the gaps stopping us, the research that would close them, and the questions still open. Every item and trial links back to the gap it advances.

  1. Stopping the immune attack

    T1D happens because the immune system destroys the body's own insulin-producing cells. Any durable cure has to stop or retrain that attack — otherwise new or replacement cells get destroyed too.

    Editorial estimate of progress30%

    Where we are today

    One therapy (teplizumab) can delay clinical onset by years in at-risk people — proof the attack can be slowed. But it's a delay, not a stop, and it works best before most cells are lost. Antigen-specific approaches that retrain immunity without blanket suppression remain unproven in people.

    What would close it

    • Antigen-specific immunotherapy that disarms only the T1D attack, sparing the rest of the immune system
    • Regulatory T-cell (Treg) therapies that re-establish tolerance
    • Combination immunotherapy timed to disease stage
    • Biomarkers that predict who responds, so treatment is targeted

    Open questions

    • Can the attack be stopped durably, not just delayed — and without lifelong immunosuppression?
    • Why do only some people respond to immune therapies, and can we tell in advance?
    • How early must you intervene to preserve enough of the body's own insulin production to matter?
    Read the full picture →

    T1D is, at root, a case of mistaken identity: the immune system tags the body's own insulin-producing cells as a threat and destroys them.1 That is why insulin replacement is a treatment, not a cure — and why simply adding new cells isn't enough on its own. Drop fresh insulin-producing cells into an unchanged immune environment and the same attack picks up where it left off.

    The first real proof that the attack is bendable arrived with teplizumab, an anti-CD3 immune therapy. In a randomized trial of at-risk relatives, a single 14-day course pushed the median time to clinical diagnosis from about 24 months on placebo to about 48 months2 — and in extended follow-up the gap widened to roughly 60 versus 27 months, with measurable preservation of beta-cell function.3 That buys years and shows the disease clock isn't fixed. But a delay is not a stop, the effect was strongest in those who still had more insulin-producing capacity left, and broad immune-modulating drugs carry their own costs.

    The goal worth ranking toward is precision: disarm the specific immune response that targets insulin-producing cells, leave the rest of the immune system intact, and make the effect durable. Antigen-specific and tolerance-restoring approaches that aim at exactly this remain unproven in people. Get there and immunotherapy stops being a way to slow the loss — and becomes the thing that protects every other cure approach.

    References

    1. DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet. 2018;391(10138):2449–2462. https://doi.org/10.1016/S0140-6736%2818%2931320-5 ↩

    2. Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019;381(7):603–613. https://doi.org/10.1056/NEJMoa1902226 ↩

    3. Sims EK, Bundy BN, Stier K, et al. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021;13(583):eabc8980. https://doi.org/10.1126/scitranslmed.abc8980 ↩

    Our take

    Teplizumab changed the conversation: it proved the timeline is bendable. The prize now is a stop, not a delay — and one precise enough that we're not trading diabetes for a suppressed immune system.

    Items working on itAlefacept (CD2 memory T-cell targeting)Baricitinib (JAK1/2 inhibitor)CELZ-201 perinatal tissue-derived cell therapyDimethyl fumarate for beta-cell preservationE-islet 01 allogeneic human regenerative isletsFrexalimab (CD40L antagonist)Golimumab (anti-TNF)Imatinib (tyrosine kinase inhibitor)Low-dose anti-thymocyte globulin (ATG)PIpepTolDC tolerogenic dendritic-cell vaccineRituximab (anti-CD20)Selective JAK inhibitors (abrocitinib / ritlecitinib)Teplizumab (Tzield)Teplizumab for new-onset T1D (Tzield)Ustekinumab (IL-12/23 p40 blocker)Verapamil (oral)
    Trials advancing itAllogeneic CD7-targeted CAR-T for T1DAllogeneic regenerative islet transplantation for brittle T1DAllogenic islet cell transplantation at University of ChicagoAutologous CD6-CAR Tregs for stage-3 T1DAutologous Tregs in T1DCARC-101C cell therapy in autoimmune T1DDiamyd GAD-alum in people at risk for T1DDimethyl fumarate for preserving beta-cell function in new-onset T1DGastrin to improve islet transplantation outcomesI-DIT: ixekizumab anti-IL-17 in new-onset T1DIMMUNOSTEM: PD-L1 gene-modified autologous HSPCsIslet transplant with T-cell depletion and gastrinIslet transplantation in brittle T1DIslet transplantation with glucocorticoid-free immunosuppressionIslet transplantation with recipient Tregs or donor bone marrowMATIN-2: teplizumab, intralymphatic insulin and low-dose IL-2Pancreatic islet transplantation into the anterior chamber of the eyePIpepTolDC tolerogenic dendritic-cell vaccinePOLARIS: GNTI-122 engineered Tregs in recent-onset T1DPrecision ATG with or without verapamil in new-onset T1DPROTECT extension: long-term teplizumab safetyRepeat BCG vaccination in established T1DRepeat BCG vaccination in pediatric T1DSanofi registry for stage 2 T1D and Tzield treatmentSequential cord-blood stem cells and islets in monogenic immunodeficiency T1DSHIELD-T1D: Shingrix and semaglutide for beta-cell preservationSingle-center phase 3 islet transplantation in non-uremic T1DSorafenib in new-onset T1DTADPOL: DFMO/polyamine pathway in recent-onset T1DTegoprubart: calcineurin-inhibitor-free islet-transplant immunosuppressionTeplizumab in Japanese stage-2 T1DTeplizumab in pediatric stage-2 T1DTregs plus anti-CD20 rituximab in pediatric stage 1 T1DTrialNet platform: teplizumab vs low-dose ATG to delay stage-3 T1DAbatacept (CTLA4-Ig) to delay type 1 diabetes in at-risk relativesASK: Autoimmunity Screening for Kids (Colorado)BANDIT: Baricitinib (JAK inhibitor) in recent-onset type 1 diabetesBARICADE-DELAY: Baricitinib to delay stage-3 T1DBARICADE-PRESERVE: Baricitinib in newly diagnosed T1DBETA PRESERVE: confirmatory teplizumab trial in recent-onset stage-3 T1DCREATE-1: CELZ-201 in recent-onset type 1 diabetesDIAGNODE-1: First intralymphatic GAD-alum dosing studyDIAGNODE-2: Intralymphatic GAD-alum (Diamyd) in recent-onset type 1 diabetesDIAGNODE-3: Intralymphatic GAD-alum in HLA DR3-DQ2 recent-onset T1DDPT-1: Diabetes Prevention Trial-Type 1 (parenteral and oral insulin)E-islet 01: allogeneic human regenerative islet therapyELSA: EarLy Surveillance for Autoimmune diabetes (UK)ENC-201-CED: Encellin encapsulated donor isletsFABULINUS: Frexalimab CD40L blockade in recent-onset T1DFr1da: General-population infant/child islet-autoantibody screening (Bavaria)Imatinib in recent-onset type 1 diabetesJAKPOT T1D: Abrocitinib and ritlecitinib in new-onset T1DLantidra (donislecel): purified allogeneic islet cell therapy (CIT-07)Low-dose anti-thymocyte globulin (ATG) ± GCSF in new-onset T1D (Haller / TrialNet)PROTECT: Teplizumab in children and adolescents with recent-onset type 1 diabetesProtégé: Anti-CD3 (teplizumab) in recent-onset type 1 diabetesRituximab-pvvr followed by abatacept in new-onset T1D (TrialNet T1D RELAY / TN25)Sana SC451: hypoimmune stem-cell-derived islets without immunosuppressionSernova Cell Pouch: implantable islet-transplant scaffoldT1DAL: Alefacept in new-onset type 1 diabetesT1GER: Golimumab in youth with new-onset type 1 diabetesTN-07: Oral insulin for prevention in autoantibody-positive relativesTN-09: Abatacept (CTLA4-Ig) in recent-onset type 1 diabetesTN-10: Teplizumab to delay clinical type 1 diabetes in at-risk relatives (Stage 2)TN-22: Hydroxychloroquine in stage 1 at-risk individualsTrialNet Pathway to PreventionUST1D2: Ustekinumab phase-2/3 in adults with recent-onset T1DUSTEKID: Ustekinumab in adolescents with recent-onset type 1 diabetesVC-01: ViaCyte first-gen encapsulated stem-cell isletsVCTX210: first CRISPR-edited, device-encapsulated stem-cell islet productVCTX211: CRISPR gene-edited hypoimmune stem-cell isletsVerapamil to preserve beta-cell function in newly diagnosed type 1 diabetes (Ver-A-T1D)VX-264: encapsulated stem-cell islets without immunosuppressionVX-880 / zimislecel: stem-cell-derived islets (with immunosuppression)

  2. A scalable supply of insulin-producing cells

    Replacing what's lost means having insulin-producing cells to transplant. Donor islets are scarce and variable; the breakthrough is growing unlimited, consistent cells from stem cells.

    Editorial estimate of progress55%

    Where we are today

    Stem-cell-derived islet therapy has produced insulin independence in early trials — a genuine milestone. The remaining supply-side problems are manufacturing consistency, scale, and cost, plus making the cells mature and safe (no stray undifferentiated cells).

    What would close it

    • Reproducible, GMP-scale differentiation of stem cells into functional islet cells
    • Quality and safety control — ensuring no undifferentiated cells remain
    • Cell sources that sidestep rejection (hypoimmune-engineered or patient-derived lines)
    • Cryopreservation and logistics for an off-the-shelf product

    Open questions

    • Can manufacturing reach the scale and price to treat millions, not dozens?
    • Which cell source wins: universal donor lines, or patient-matched?
    • How mature must lab-grown cells be to regulate glucose like the real thing?
    Read the full picture →

    You can't replace what's been destroyed without a source of replacements. For decades that source was donor pancreases — and conventional islet transplantation is constrained by donor scarcity, variable graft quality, and the need for lifelong immunosuppression.1 As a cure for a disease affecting millions, it was never going to scale.

    Stem cells changed the math. We can now coax stem cells into insulin-producing islet cells in the lab, in principle without limit, and early trials have shown recipients producing their own insulin again — some free of injections entirely. In the zimislecel (VX-880) phase 1–2 trial, all 12 full-dose recipients made glucose-responsive insulin and hit standard glucose targets at one year — HbA1c below 7%, more than 70% time-in-range — and 10 of 12 (83%) no longer needed insulin at all.2 That is one of the most important results in the history of T1D.

    What's left is industrialization: making the cells the same way every time, proving none are left in an immature or risky state, and driving the cost down far enough to matter.3 The supply problem is closer to solved than any other cure gap — which is exactly why protecting those cells from the immune system is now the rate-limiting step.

    References

    1. Strakosch T, Forbes S. "Navigating the immunological and logistical transformation brought by stem cell-derived islets for the treatment of type 1 diabetes" (UK key-opinion-leader perspective). Diabetic Medicine 2026. Notes that conventional islet transplantation is limited by donor scarcity, variable graft quality, and lifelong immunosuppression, and frames stem-cell-derived islets as a scalable, standardised alternative. https://doi.org/10.1111/dme.70230 ↩

    2. Reichman TW, et al. "Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes" (zimislecel / VX-880 phase 1–2). New England Journal of Medicine 2025;393(9):858–868 (20 June 2025). All 12 full-dose recipients achieved glucose-responsive C-peptide, HbA1c <7% and time-in-range >70% at one year; 10/12 became insulin-independent — all still on immunosuppression. https://doi.org/10.1056/NEJMoa2506549 ↩

    3. Rajaei B, et al. "Clinically compliant enrichment of human pluripotent stem cell-derived islets." Science Translational Medicine 2025;17(792):eadl4390. A scalable, manufacturing-compatible purification step that removes non-target cell types from the final stem-cell-derived islet product. https://doi.org/10.1126/scitranslmed.adl4390 ↩

    Our take

    This is the cure gap with the most visible momentum. Insulin independence from lab-grown cells has happened in humans. The fight has moved from "can we make the cells" to "can we make them by the million, safely, and protect them" — see encapsulation and the immune attack.

    Items working on itE-islet 01 allogeneic human regenerative islets
    Trials advancing itAllogeneic regenerative islet transplantation for brittle T1DAllogenic islet cell transplantation at University of ChicagoAutologous insulin-producing mesenchymal stem cells in youthCelregen CRG-002 allogeneic iPSC-derived isletsIslet transplantation in brittle T1DOPF-310 encapsulated porcine islets for unstable T1DRGB-5088 islet cell injection in T1DSequential cord-blood stem cells and islets in monogenic immunodeficiency T1DSeraxis SR-02 pancreatic endocrine cells in adult T1DE-islet 01: allogeneic human regenerative islet therapyLantidra (donislecel): purified allogeneic islet cell therapy (CIT-07)Sana SC451: hypoimmune stem-cell-derived islets without immunosuppressionSernova Cell Pouch: implantable islet-transplant scaffoldVC-01: ViaCyte first-gen encapsulated stem-cell isletsVCTX210: first CRISPR-edited, device-encapsulated stem-cell islet productVCTX211: CRISPR gene-edited hypoimmune stem-cell isletsVX-264: encapsulated stem-cell islets without immunosuppressionVX-880 / zimislecel: stem-cell-derived islets (with immunosuppression)

  3. Protecting cells without lifelong immunosuppression

    Transplanted cells face two enemies: the original autoimmune attack and ordinary transplant rejection. Today the defense is immunosuppressant drugs for life — which is why cell therapy is reserved for the most severe cases. Remove that requirement and a cure opens to everyone.

    Editorial estimate of progress35%

    Where we are today

    Two routes are racing: physically encapsulating cells behind a membrane that blocks immune cells while letting glucose and insulin through, and gene-editing the cells to be invisible to the immune system ("hypoimmune"). Both work in principle; the open problems are oxygen, fibrosis, and proving the protection is complete and durable.

    What would close it

    • Encapsulation devices and materials that resist fibrosis and keep cells oxygenated
    • Hypoimmune cell engineering that evades rejection AND autoimmunity without drugs
    • Retrievable, refillable implant designs
    • Local immune modulation at the implant site instead of body-wide drugs

    Open questions

    • Can a membrane keep cells alive (oxygen!) and hidden for years, not months?
    • Does gene-edited immune evasion hold up against the specific T1D attack, not just generic rejection?
    • If protection fails silently, how does the person know before the graft is lost?
    Read the full picture →

    Here is the cruel catch in cell-replacement therapy: the cells work, but keeping them alive means suppressing the immune system for life. The drugs carry real risks — infection, cancer, organ strain — heavy enough that the therapy is reserved for people with the most dangerous, uncontrollable T1D. The cure exists; it's just locked behind a trade most people shouldn't make.

    Removing immunosuppression is the gate. Two approaches are pushing on it. Encapsulation wraps the cells behind a barrier with pores small enough to stop immune cells but large enough to pass glucose in and insulin out — a physical shield. Hypoimmune engineering edits the cells themselves so the immune system never recognizes them as foreign — a chemical cloak.

    Both face hard problems. Encapsulated cells can suffocate or get walled off by scar tissue — Vertex's lead device candidate, VX-264, was safe but failed to raise insulin production enough to help, and was discontinued in 2025.1 Engineered cells must evade not just ordinary rejection but the specific, relentless autoimmune attack that started the disease — yet here the first signals are encouraging: in non-human primates, hypoimmune gene-edited islets reached insulin independence with no immunosuppression,2 and a first-in-human case has now shown such cells surviving and secreting insulin (C-peptide) in a person with T1D taking no immunosuppression at all.3 Both encapsulation and hypoimmune editing are widely framed as the routes to cut the immunosuppression that has held beta-cell replacement back.4 Whoever solves protection — fully, durably, drug-free — turns a niche procedure into a cure the whole T1D population can actually have.

    References

    1. Vertex's lead encapsulation candidate VX-264 — islet cells inside an immunoprotective device requiring no immunosuppression — was safe but did not raise C-peptide enough to benefit patients, and was discontinued in 2025. Vertex Pharmaceuticals, "Vertex Announces Program Updates for its Type 1 Diabetes Portfolio" (2025). https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-program-updates-type-1-diabetes-portfolio ↩

    2. In a fully immunocompetent, diabetic non-human primate, allogeneic hypoimmune (B2M and CIITA knockout, CD47 overexpression) islets engrafted and provided stable insulin independence with no detectable immune response and no immunosuppression — preclinical proof of the "cloak" approach. Hu X, et al., "Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate," Cell Stem Cell (2024). https://doi.org/10.1016/j.stem.2024.02.001 ↩

    3. First-in-human case report: hypoimmune (HIP) gene-edited allogeneic islet cells survived and secreted insulin (C-peptide), responding to a meal, in a person with type 1 diabetes without any immunosuppression — an early but important clinical signal for the "cloak" approach. "Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression," New England Journal of Medicine (2025). https://doi.org/10.1056/NEJMoa2503822 ↩

    4. A 2025 review of the field describes encapsulation and gene editing to create hypoimmune cells as the strategies that "could reduce the need for immunosuppression that has hampered β-cell replacement." Ziegler AG, Cengiz E, Kay TWH, "The future of type 1 diabetes therapy," Lancet (2025). https://doi.org/10.1016/S0140-6736%2825%2901438-2 ↩

    Our take

    This is the true gate on a universal cure. We have cells that work and a growing supply of them; what we don't yet have is a way to protect them that's good enough to skip the immunosuppression. Crack this and cell therapy stops being a last resort and starts being *the* treatment.

    Trials advancing itOPF-310 encapsulated porcine islets for unstable T1DSeraxis SR-02 pancreatic endocrine cells in adult T1DAbatacept (CTLA4-Ig) to delay type 1 diabetes in at-risk relativesDIAGNODE-1: First intralymphatic GAD-alum dosing studyDIAGNODE-2: Intralymphatic GAD-alum (Diamyd) in recent-onset type 1 diabetesDPT-1: Diabetes Prevention Trial-Type 1 (parenteral and oral insulin)ENC-201-CED: Encellin encapsulated donor isletsLantidra (donislecel): purified allogeneic islet cell therapy (CIT-07)Low-dose anti-thymocyte globulin (ATG) ± GCSF in new-onset T1D (Haller / TrialNet)PROTECT: Teplizumab in children and adolescents with recent-onset type 1 diabetesProtégé: Anti-CD3 (teplizumab) in recent-onset type 1 diabetesRituximab-pvvr followed by abatacept in new-onset T1D (TrialNet T1D RELAY / TN25)Sana SC451: hypoimmune stem-cell-derived islets without immunosuppressionSernova Cell Pouch: implantable islet-transplant scaffoldTN-07: Oral insulin for prevention in autoantibody-positive relativesTN-09: Abatacept (CTLA4-Ig) in recent-onset type 1 diabetesTN-10: Teplizumab to delay clinical type 1 diabetes in at-risk relatives (Stage 2)TN-22: Hydroxychloroquine in stage 1 at-risk individualsVC-01: ViaCyte first-gen encapsulated stem-cell isletsVCTX210: first CRISPR-edited, device-encapsulated stem-cell islet productVCTX211: CRISPR gene-edited hypoimmune stem-cell isletsVerapamil to preserve beta-cell function in newly diagnosed type 1 diabetes (Ver-A-T1D)VX-264: encapsulated stem-cell islets without immunosuppressionVX-880 / zimislecel: stem-cell-derived islets (with immunosuppression)

  4. Finding it early enough to act

    The interventions that preserve the body's own insulin production work best before most cells are gone — but most people are diagnosed only at crisis, in the ER, with little left to save. You can't protect what's already destroyed.

    Editorial estimate of progress45%

    Where we are today

    A simple autoantibody test can identify T1D years before symptoms and stage how far it's progressed. General-population screening programs are expanding, and early detection already slashes dangerous DKA-at-diagnosis. But screening is still far from universal, so the therapeutic window is usually missed.

    What would close it

    • Low-cost, scalable screening (home and capillary tests) for the general population, not just relatives
    • Integrating screening into routine pediatric and primary care
    • Better staging and progression prediction to time interventions
    • Linking a positive screen directly to monitoring and trial access

    Open questions

    • How do you screen a whole population affordably and equitably?
    • How often must someone at risk be re-tested as the disease evolves?
    • Can we predict not just *if* but *when* clinical onset will hit?
    Read the full picture →

    There's a window in T1D when intervention pays off most: while the body still has a meaningful share of its insulin-producing cells. Protect them then and a person may keep partial insulin production for years — easier control, fewer complications, more time for better cures to arrive. Miss it and you're rebuilding from zero.

    The tragedy is that most people are found at the very end of that window — diagnosed in the emergency room, often in diabetic ketoacidosis, with little left to save. Yet a simple test for autoantibodies can flag the disease years earlier and even stage how far along it is.

    The gap is reach. Screening has mostly been offered to relatives of people with T1D — but roughly 90% of new cases have no family history, so that misses the majority.1 Universal, low-cost screening built into routine care would change who gets found, and when: in the Bavarian Fr1da program, children identified pre-symptomatically had DKA at clinical onset in only ~2.5% of cases — far below the roughly 20–48% range reported at unscreened clinical onset.2 It's the cheapest intervention on this page, and it's the one that makes every other cure-strand advance actually reachable for real people.

    References

    1. Approximately 90% of people who develop T1D have no first-degree relative with the disease, so screening only relatives misses most future cases — a key rationale for general-population screening. Sims EK, et al. "Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective." Diabetes 71(4):610–623 (2022). https://doi.org/10.2337/dbi20-0054 ↩

    2. The Fr1da study screened 90,632 Bavarian children for islet autoantibodies in routine primary care, detecting presymptomatic T1D at 0.31% prevalence with only 2 cases of DKA among those identified. Ziegler A-G, et al. "Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany." JAMA 323(4):339–351 (2020). https://doi.org/10.1001/jama.2019.21565. Children diagnosed pre-symptomatically then went on to milder clinical onset, with DKA in only 2.5% versus the ~20–48% generally reported at unscreened clinical onset. Hummel S, et al. "Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation." Diabetologia 66(9):1633–1642 (2023). https://doi.org/10.1007/s00125-023-05953-0 ↩

    Our take

    The most underrated lever on the whole cure roadmap, because it multiplies everything else: every prevention therapy, every cell-preserving immunotherapy, is only as useful as our ability to find people while they still have something to preserve. Screening is cheap. Missing the window is not.

    Items working on itASK (Autoimmunity Screening for Kids)Low-dose anti-thymocyte globulin (ATG)Oral glucose tolerance test (OGTT) for T1D stagingRituximab (anti-CD20)Teplizumab (Tzield)
    Trials advancing itDiamyd GAD-alum in people at risk for T1DGLP-1 receptor agonist for stage-1 T1DGLP-1RA added around teplizumab in stage-2 T1DGTT@Home: home oral glucose tolerance testing for T1D screeningQuebec screening program for relatives of people with T1DSanofi registry for stage 2 T1D and Tzield treatmentTeplizumab in Japanese stage-2 T1DTeplizumab in pediatric stage-2 T1DTregs plus anti-CD20 rituximab in pediatric stage 1 T1DTrialNet platform: teplizumab vs low-dose ATG to delay stage-3 T1DType 1 diabetes screening in pediatric primary careAbatacept (CTLA4-Ig) to delay type 1 diabetes in at-risk relativesASK: Autoimmunity Screening for Kids (Colorado)BARICADE-DELAY: Baricitinib to delay stage-3 T1DDPT-1: Diabetes Prevention Trial-Type 1 (parenteral and oral insulin)ELSA: EarLy Surveillance for Autoimmune diabetes (UK)Fr1da: General-population infant/child islet-autoantibody screening (Bavaria)Protégé: Anti-CD3 (teplizumab) in recent-onset type 1 diabetesTN-07: Oral insulin for prevention in autoantibody-positive relativesTN-10: Teplizumab to delay clinical type 1 diabetes in at-risk relatives (Stage 2)TN-22: Hydroxychloroquine in stage 1 at-risk individualsTrialNet Pathway to Prevention

  5. Making a cure last a lifetime

    A cure that fades in a few years is a reprieve, not a cure. Restored insulin production has to survive the ongoing autoimmunity, the wear on the cells, and the years — ideally for decades, ideally once.

    Editorial estimate of progress20%

    Where we are today

    Early islet and stem-cell results show function can be restored; how long it lasts at scale, and whether it holds without continuous drugs, is still being learned. Regeneration and gene approaches that could refresh or renew cells in place are earlier still.

    What would close it

    • Long-term follow-up on graft survival and insulin independence
    • Regeneration — coaxing the body to regrow its own insulin-producing cells
    • Strategies to refresh or top up grafts non-invasively over time
    • Protecting restored cells from the same autoimmunity that caused T1D

    Open questions

    • How many years can a single cell-replacement procedure last?
    • Can the body be made to regenerate insulin-producing cells durably on its own?
    • Is "functional cure" (stable, drug-light control) the realistic near-term goal, with one-and-done further out?
    Read the full picture →

    The word "cure" carries a promise: not just that something works, but that it lasts. For T1D that bar is steep. Whatever restores insulin production has to withstand the autoimmunity that caused the disease in the first place, the ordinary aging and exhaustion of working cells, and simply the passage of decades. A therapy that delivers two good years is a meaningful treatment — but calling it a cure would be the kind of overstatement this site exists to avoid. The most advanced cell therapy so far, zimislecel, has reported glucose-responsive insulin production durable only through about one year of follow-up — promising, but nowhere near the decades a true cure implies.1

    There's a useful distinction here. A functional cure means stable, near-normal glucose with little or no day-to-day burden — even if it leans on a long-lived implant or occasional drugs. A complete cure means the body simply regulates glucose on its own again, indefinitely, ideally from a single intervention. The first is within sight; the second is the longer horizon, where regeneration and gene approaches live — and where the recurring obstacles are durable graft survival and the immune system, both the original autoimmunity and the response to the transplant itself.2

    Durability is also where intellectual honesty matters most. Early results deserve excitement, not coronation. Our job is to show how long each approach has actually been shown to last — and to rank a lasting answer above a temporary one, every time.

    References

    1. In the zimislecel (VX-880) phase 1–2 trial, all 14 participants engrafted and produced C-peptide, and 10 of 12 who received the full dose were insulin-independent at day 365; the authors describe this as a "small, short-term study," with islet function followed through about one year — the longest reported data for a stem-cell islet therapy and a reminder that long-term durability is still unproven. Reichman TW, et al. New England Journal of Medicine (2025). https://doi.org/10.1056/NEJMoa2506549 ↩

    2. Reviews of the field place sustained, long-term graft function and freedom from chronic immunosuppression as the "next frontier," with strategies such as immune-isolation, immune-privileged sites, immune-evasive gene editing, and tolerance induction all still under investigation. Hering BJ, Rickels MR, et al., "Advances in Cell Replacement Therapies for Diabetes," Diabetes (2025). https://doi.org/10.2337/db25-0037 — and across recent trials, durable insulin independence and immune rejection remain the key unsolved challenges: Lin TM, et al., Diabetes & Metabolism (2026). https://doi.org/10.1016/j.diabet.2026.101738 ↩

    Our take

    The honesty gap. It's tempting to call the first insulin-independence results a cure — but durability is unproven, and saying so plainly is the whole point of this site. We rank a five-year fix below a lifetime one, and we say which is which.

    Items working on itAlefacept (CD2 memory T-cell targeting)CELZ-201 perinatal tissue-derived cell therapyDimethyl fumarate for beta-cell preservationE-islet 01 allogeneic human regenerative isletsFrexalimab (CD40L antagonist)Golimumab (anti-TNF)Imatinib (tyrosine kinase inhibitor)Selective JAK inhibitors (abrocitinib / ritlecitinib)Teplizumab for new-onset T1D (Tzield)Ustekinumab (IL-12/23 p40 blocker)Verapamil (oral)
    Trials advancing itAllogeneic regenerative islet transplantation for brittle T1DAllogenic islet cell transplantation at University of ChicagoAutologous insulin-producing mesenchymal stem cells in youthCARC-101C cell therapy in autoimmune T1DCelregen CRG-002 allogeneic iPSC-derived isletsDenosumab for beta-cell function in T1DDimethyl fumarate for preserving beta-cell function in new-onset T1DGastrin to improve islet transplantation outcomesGLP-1 receptor agonist for stage-1 T1DGLP-1RA added around teplizumab in stage-2 T1DI-DIT: ixekizumab anti-IL-17 in new-onset T1DIMMUNOSTEM: PD-L1 gene-modified autologous HSPCsIslet transplant with T-cell depletion and gastrinIslet transplantation in brittle T1DIslet transplantation with glucocorticoid-free immunosuppressionIslet transplantation with recipient Tregs or donor bone marrowMATIN-2: teplizumab, intralymphatic insulin and low-dose IL-2MTX228 adaptive phase 2 study in T1DOPF-310 encapsulated porcine islets for unstable T1DPancreatic islet transplantation into the anterior chamber of the eyePOLARIS: GNTI-122 engineered Tregs in recent-onset T1DPrecision ATG with or without verapamil in new-onset T1DPROTECT extension: long-term teplizumab safetyRepeat BCG vaccination in established T1DRepeat BCG vaccination in pediatric T1DRGB-5088 islet cell injection in T1DSanofi registry for stage 2 T1D and Tzield treatmentSequential cord-blood stem cells and islets in monogenic immunodeficiency T1DSeraxis SR-02 pancreatic endocrine cells in adult T1DSHIELD-T1D: Shingrix and semaglutide for beta-cell preservationSingle-center phase 3 islet transplantation in non-uremic T1DSorafenib in new-onset T1DTADPOL: DFMO/polyamine pathway in recent-onset T1DTegoprubart: calcineurin-inhibitor-free islet-transplant immunosuppressionTregs plus anti-CD20 rituximab in pediatric stage 1 T1DVerapamil to preserve residual insulin secretion in childrenAbatacept (CTLA4-Ig) to delay type 1 diabetes in at-risk relativesBANDIT: Baricitinib (JAK inhibitor) in recent-onset type 1 diabetesBARICADE-PRESERVE: Baricitinib in newly diagnosed T1DBETA PRESERVE: confirmatory teplizumab trial in recent-onset stage-3 T1DCREATE-1: CELZ-201 in recent-onset type 1 diabetesDIAGNODE-1: First intralymphatic GAD-alum dosing studyDIAGNODE-2: Intralymphatic GAD-alum (Diamyd) in recent-onset type 1 diabetesDIAGNODE-3: Intralymphatic GAD-alum in HLA DR3-DQ2 recent-onset T1DE-islet 01: allogeneic human regenerative islet therapyENC-201-CED: Encellin encapsulated donor isletsFABULINUS: Frexalimab CD40L blockade in recent-onset T1DImatinib in recent-onset type 1 diabetesJAKPOT T1D: Abrocitinib and ritlecitinib in new-onset T1DLantidra (donislecel): purified allogeneic islet cell therapy (CIT-07)Low-dose anti-thymocyte globulin (ATG) ± GCSF in new-onset T1D (Haller / TrialNet)PROTECT: Teplizumab in children and adolescents with recent-onset type 1 diabetesProtégé: Anti-CD3 (teplizumab) in recent-onset type 1 diabetesRituximab-pvvr followed by abatacept in new-onset T1D (TrialNet T1D RELAY / TN25)Sana SC451: hypoimmune stem-cell-derived islets without immunosuppressionSernova Cell Pouch: implantable islet-transplant scaffoldT1DAL: Alefacept in new-onset type 1 diabetesT1GER: Golimumab in youth with new-onset type 1 diabetesTN-09: Abatacept (CTLA4-Ig) in recent-onset type 1 diabetesUST1D2: Ustekinumab phase-2/3 in adults with recent-onset T1DUSTEKID: Ustekinumab in adolescents with recent-onset type 1 diabetesVC-01: ViaCyte first-gen encapsulated stem-cell isletsVCTX210: first CRISPR-edited, device-encapsulated stem-cell islet productVCTX211: CRISPR gene-edited hypoimmune stem-cell isletsVerapamil to preserve beta-cell function in newly diagnosed type 1 diabetes (Ver-A-T1D)VX-264: encapsulated stem-cell islets without immunosuppressionVX-880 / zimislecel: stem-cell-derived islets (with immunosuppression)