For the first time in years, Amanda Smith does not carry insulin.
The 36-year-old nurse and mother from London, Ontario, was part of a small but clinical trial that has quietly shifted what scientists believe is possible in the fight against Type 1 diabetes.
In a study published in the New England Journal of Medicine, researchers reported that 10 out of 12 patients who received a single dose of lab-grown stem cells were completely free of insulin injections after one year.
The therapy, called zimislecel and developed by Vertex Pharmaceuticals, works by introducing specially grown insulin-producing cells directly into the body, where they settle in the liver and begin doing what the pancreas can no longer do on its own.
The results were presented at the American Diabetes Association’s 85th Scientific Sessions in Chicago and immediately caught the attention of the global medical community.
“I remember being scared and excited, and it’s history now,” Smith said of the day she stopped taking insulin, August 1, nearly two years ago.
The trial
The clinical trial, known as the FORWARD-101 study, enrolled patients with a specific and particularly dangerous profile of Type 1 diabetes.
These were people living with long-standing, hard-to-manage Type 1 diabetes who also experienced severe hypoglycemic events, sudden and dangerous drops in blood sugar that can cause seizures, unconsciousness, and in some cases, death.
All 12 participants who received the full dose had experienced at least two such episodes in the year before the trial began.
Zimislecel is described as an allogeneic therapy, meaning the cells do not come from the patient’s own body but are manufactured in a lab from pluripotent stem cells, which are cells capable of becoming virtually any cell type.
In this case, those stem cells were guided to become fully differentiated pancreatic islet cells, the same clusters of cells found in a healthy pancreas that produce insulin in response to rising blood sugar.
Each participant received a single infusion of 0.8 billion cells delivered directly into the portal vein, the large blood vessel that carries blood from the gut to the liver.
Once there, the cells were expected to engraft, meaning to take up residence and begin functioning.
All participants were also placed on glucocorticoid-free immunosuppressive therapy, a type of medication designed to prevent the body’s immune system from attacking the new cells.
This is important because Type 1 diabetes is itself an autoimmune condition, meaning the immune system has already destroyed the body’s original insulin-producing cells and would likely attempt to destroy any new ones without suppression.
The trial ran under an open-label, five-year design, with the Phase 1/2 results now available covering at least one year of follow-up for all 12 patients.
Findings from the trial
The results were striking across every measurement researchers tracked.
All 12 participants showed successful engraftment, meaning the transplanted cells established themselves in the liver and began producing insulin in a glucose-responsive way, rising when blood sugar rose and falling appropriately when it came down.
This is called physiologic islet function, and it is what the body is supposed to do naturally.
Ten of the 12 participants, or 83%, were completely free of exogenous insulin at the one-year mark.
Of the remaining two participants, both showed dramatically reduced insulin needs, with the entire group seeing a mean reduction in daily insulin dose of 92%.
Every participant achieved an HbA1c level below 7%, which is the standard clinical target for good blood sugar management, and maintained a time-in-range above 70%, meaning blood sugar stayed within the healthy range for at least 70% of each day.
Perhaps most meaningfully for this particular group of patients, severe hypoglycemic events disappeared entirely.
From day 90 onward, not a single participant experienced another episode of dangerous low blood sugar.
For people who had been living with the constant threat of sudden collapse, that alone represents an extraordinary change in daily life.
Two participants passed away during the study period, though both deaths were determined by researchers to be unrelated to the zimislecel treatment itself and consistent with complications arising from long-standing diabetes.
The therapy’s safety profile was otherwise consistent with the known effects of immunosuppression and the infusion procedure.
What Most People Get Wrong About Stem Cell Therapy for Diabetes
Here is where the story gets more complicated, and more interesting.
When most people hear “stem cells,” they picture something experimental, risky, and decades away from real-world use.
The truth is quite different.
The scientific roots of this treatment stretch back 25 years to Canada itself.
In the late 1990s, researchers in Alberta pioneered what became known as the Edmonton Protocol, a technique that involved taking insulin-producing islet cells from deceased organ donors and transplanting them into people with hard-to-manage Type 1 diabetes.
It worked.
According to the University of Alberta, more than 2,500 patients around the world were treated using this method, and roughly 80% were able to stop taking insulin injections entirely, at least for a period of time.
But there was a wall that researchers could not get past.
There simply were not enough organ donors.
Two or three donor pancreases were typically needed to treat a single patient.
The number of available pancreases was always far smaller than the number of people who needed help.
On top of that, patients required lifelong immunosuppression, which carries its own risks including higher susceptibility to infection and certain cancers.
The Edmonton Protocol was a proof of concept.
It showed the body could accept new islet cells and use them to produce insulin.
What it could not do was scale.
This is where zimislecel changes the equation.
Because the cells are manufactured from stem cells in a laboratory rather than harvested from donors, there is no donor shortage.
The treatment can, in theory, be produced at scale and made available to far more people.
The University Health Network in Toronto became the first Canadian centre to deliver zimislecel as part of this international trial, a full-circle moment for a country that gave the world the original islet transplant concept.
How it applies to real life
Type 1 diabetes affects roughly nine million people worldwide, and unlike Type 2 diabetes, it cannot be managed through diet or lifestyle changes alone.
It is an autoimmune disease.
The immune system attacks and destroys the beta cells in the pancreas, permanently eliminating the body’s ability to produce insulin.
From the moment of diagnosis, most patients enter a lifelong routine of injections, glucose monitoring, carbohydrate counting, and careful management of every meal, every bout of exercise, every illness, and every hour of sleep.
Studies have consistently shown that people with Type 1 diabetes carry a significantly higher risk of anxiety and depression than the general population, in large part because the disease never pauses.
Severe hypoglycemia adds another layer of threat.
A blood sugar crash can happen while driving, while sleeping, or while caring for children.
It can become fatal with very little warning.
For the patients in the FORWARD trial, all of whom had experienced multiple such episodes in the year before enrolling, the elimination of hypoglycemic events may be as significant as the elimination of insulin dependency.
In practical terms, what zimislecel offers is the restoration of something closer to a normal relationship with one’s own body.
Amanda Smith, who still monitors her blood sugar as a precaution, describes the change in terms that no clinical endpoint can fully capture.
She celebrates August 1 as the day she stepped out of a routine that had defined her daily existence for years.
What Comes Next
The FORWARD trial is ongoing and has now moved into Phase 3, with enrollment targeting approximately 50 participants and expected to complete dosing throughout 2025.
Vertex Pharmaceuticals has also announced plans to initiate a separate study evaluating zimislecel in adults with Type 1 diabetes who have already received kidney transplants and are therefore already taking immunosuppressive medication, a population where the therapy’s risk-benefit profile may be particularly favorable.
Regulatory submissions are anticipated in 2026, which would be the first step toward making zimislecel available outside of clinical trials.
There are still important questions that need answering. How long does the benefit last?
The one-year data are encouraging, but Type 1 diabetes is a lifelong condition, and researchers need to understand whether the transplanted cells continue functioning over five, ten, or twenty years.
The ongoing five-year FORWARD study is designed in part to answer that.
The requirement for lifelong immunosuppression also remains a limitation.
While the glucocorticoid-free regimen used in this trial carries fewer risks than older immunosuppression protocols, it still increases vulnerability to infections and requires careful management.
Researchers across multiple institutions are working on approaches that could eventually eliminate this requirement, including encapsulation technologies that would shield the transplanted cells from immune attack without suppressing the entire immune system.
Those approaches are still in earlier stages of development.
What this study does establish, clearly and with peer-reviewed evidence, is that manufactured stem cells can restore insulin production in people with Type 1 diabetes, at a success rate that would have seemed implausible not long ago.
The fact that the benefit arrived from a single infusion, rather than a lifelong treatment regimen, is not a footnote.
It is the entire point.
A Shift in What Feels Possible
Science moves in increments, and the story of diabetes treatment is a long chain of increments.
Frederick Banting and Charles Best discovered insulin in 1921 in Toronto, saving millions of lives.
The Edmonton Protocol in the late 1990s showed that new islet cells could work inside a human body.
Now, a century after insulin was first isolated just down the road from where Amanda Smith lives, a lab-grown version of the cells that produce it has given her back her August 1st.
That is, as she put it, history. The FORWARD trial is not the end of the story.
It is closer to a proof that the story can have a different ending than the one millions of people with Type 1 diabetes have been living.
For researchers, the results call for continued investigation in larger, more diverse populations.
For patients, they represent something harder to measure but just as real: a reason to keep watching what comes next.
The Immunosuppression Question Nobody Can Ignore
There is one part of this story that deserves more attention than it typically receives.
Every patient in the FORWARD trial was placed on lifelong immunosuppressive medication to prevent the body from rejecting the newly transplanted cells.
That is not a small ask.
Long-term immunosuppression carries serious risks, including opportunistic infections, kidney toxicity, and a higher likelihood of developing certain cancers.
For some patients, those trade-offs are clearly worth it.
People who have already experienced multiple life-threatening hypoglycemic events are living with a threat that is immediate and real.
Trading that threat for the managed risks of immunosuppression is, for them, a straightforward calculation.
But it does mean that zimislecel, in its current form, is not a treatment designed for everyone with Type 1 diabetes.
It is designed for a specific subset of patients whose disease is severe enough that the benefits plainly outweigh the burdens.
That distinction matters as the therapy moves toward regulatory review.
What Researchers Are Working on Next
The good news is that scientists are not standing still on this problem.
Innovations such as encapsulation devices, hypoimmunogenic stem cells, and immunomodulatory strategies are being developed specifically to reduce or eliminate the need for lifelong immune suppression after islet transplantation.
The basic idea behind encapsulation is elegant.
Instead of suppressing the entire immune system, you wrap the transplanted cells in a protective barrier that lets insulin and nutrients pass through while keeping immune cells out.
Think of it like a tiny, porous shield built around each cluster of transplanted cells.
Emerging strategies including microencapsulation, nanoencapsulation, and hypoimmune engineering are being explored to protect transplanted islets from immune attack and potentially eliminate the need for immunosuppression altogether.
Vertex itself tested an encapsulated version of its therapy, called VX-264, but that trial was ultimately discontinued after it failed to meet its efficacy endpoint.
That setback does not close the door.
It simply means the current generation of encapsulation technology is not yet ready, while the cell therapy itself clearly is.
The parallel tracks of research happening right now suggest that in the coming decade, a version of this treatment that requires no immunosuppression at all is a realistic scientific goal.
Regulatory Approval Is Closer Than It Sounds
Vertex has confirmed it expects to file for global regulatory approval of zimislecel in 2026, which would be the first step toward making it available outside of clinical trials.
That timeline is relatively fast by the standards of medical innovation.
It reflects both the strength of the clinical data and the regulatory designations the therapy has already earned.
Zimislecel has been granted Regenerative Medicine Advanced Therapy and Fast Track designations from the US Food and Drug Administration, Priority Medicines designation from the European Medicines Agency, and an Innovation Passport from the UK’s Medicines and Healthcare products Regulatory Agency.
Each of those designations is a signal that regulators are taking this therapy seriously and have committed to expedited review processes.
If submissions go as planned in 2026, real-world access for qualifying patients could follow within a few years of that.
The Bigger Picture for Millions of People
Type 1 diabetes is not rare.
According to the International Diabetes Federation, approximately 8.75 million people worldwide are living with Type 1 diabetes, and the number continues to rise.
For most of them, the daily reality of the disease involves more than injections.
It involves a constant mental load.
Every carbohydrate, every workout, every glass of wine, every stressful meeting at work has the potential to send blood sugar in the wrong direction.
Continuous glucose monitors and insulin pumps have made that management easier in recent years, but they have not changed the fundamental nature of the disease.
The immune system destroyed the beta cells.
No device changes that.
What zimislecel attempts to change is that foundational reality.
It does not manage the disease from the outside.
It replaces the cells the immune system took away.
That is a categorically different approach, and the data now suggest it can work.
One More Detail Worth Sitting With
The cells used in this therapy are manufactured from pluripotent stem cells, which means they are grown in a laboratory rather than harvested from a donor.
That is not just a logistical convenience.
It is the reason this approach can potentially scale.
The Edmonton Protocol, which helped over 2,500 patients worldwide, ran into a wall because donor pancreases are scarce.
With zimislecel, the raw material is grown in a controlled lab environment.
There is no waiting list for a donor.
There is no geographic bottleneck based on organ availability.
If the manufacturing process is reliable and the regulatory pathway clears, the treatment could, in principle, be made available to any qualifying patient anywhere in the world.
Researchers at the University Health Network in Toronto, which was the first Canadian center to deliver zimislecel as part of this international trial, have described the results as a milestone that would not have been imaginable a generation ago.
They are not wrong.
The Distance Between a Trial and a Treatment
It is worth being honest about where we are.
Twelve patients is a small number.
The five-year FORWARD study is still ongoing, and researchers still need to confirm that the transplanted cells keep working over the long haul.
The immunosuppression requirement is a real limitation for millions of people who would otherwise be candidates.
And regulatory approvals, while anticipated, are not guaranteed.
None of that diminishes what has already been shown.
A single infusion of lab-grown cells restored the body’s ability to produce insulin in 83% of patients, eliminated dangerous blood sugar crashes entirely, and did so with a safety profile that, while not trivial, is manageable.
For a disease that has asked so much of so many people for so long, that is a result worth paying close attention to.
The next few years will determine whether this becomes a treatment that reaches patients at scale.
But the science, right now, is pointing somewhere that was not visible even a decade ago.
That is worth following.
Sources and Further Reading
The Conversation: People With Severe Diabetes Cured in Small Stem Cell Trial
