For people with type 1 diabetes, daily life can feel like a relentless numbers game: tracking blood sugar, adjusting insulin, bracing for highs and lows, and watching for signs of the next crash. Even the best technology, including pumps, sensors, closed-loop systems, can’t fully replicate the natural rhythm of a healthy pancreas.
But a new study suggests an innovative approach: instead of working around the damage, what if you could mass-produce and replace what’s missing?
A small clinical trial, published in The New England Journal of Medicine in June, tested a therapy called zimislecel: stem cell–derived islet cells infused into the liver. In 12 people with severe, long-standing type 1 diabetes, these lab-grown cells began producing insulin again, improving blood sugar control, preventing dangerous lows, and, in most cases, eliminating the need for insulin.
It’s early days and challenges remain. But for a condition where every treatment has meant compromise, zimislecel hints at something different: a way to restore what the disease took away, this time without relying on donor organs.
Limits of insulin
Type 1 diabetes is a disease of loss. It begins when the immune system attacks the pancreas’s islets cells, which produce insulin and other hormones that regulate blood sugar. Without those cells, people rely on external insulin, adjusting doses by trial and error.
But this approach has limits. Despite automated delivery systems, many people still struggle. About 75% don’t reach their recommended blood sugar targets and some continue to experience episodes of low levels that can cause seizures, unconsciousness or worse.
The idea of replacing lost islets isn’t new. Transplants from deceased donors have reduced or eliminated insulin use in some patients. However, as it stands today, the procedure is limited by several practical and logistical hurdles, Nihal Thomas, professor of endocrinology and head of the Centre for Stem Cell Research at Christian Medical College, Vellore, said.
“Once the pancreas is removed, the clock starts ticking: it has to be processed quickly while it’s still cold and viable,” Prof. Thomas said. “Extracting the islets isn’t straightforward either. You need a Ricordi chamber, a skilled lab team, and, even then, one pancreas may not give you enough. The actual infusion is not that complex, but everything that leads up to it makes the process demanding.”
A way to rebuild islets
Instead of harvesting islets from donors, scientists made zimislecel by growing islets from pluripotent stem cells in the lab. These are matured into functioning islets and infused into the hepatic portal vein. The hope is that these cells will take root, survive, and begin producing insulin from within the body.
The trial enrolled people with the most severe forms of the disease: all had lived with type 1 diabetes for more than two decades, had no detectable insulin production, and had experienced two to four severe hypoglycaemic events in the previous year. Even with intensive insulin therapy and continuous glucose monitoring, control was poor.
All 12 participants received a full dose of zimislecel and were followed up for at least a year. To prevent their bodies from rejecting the transplanted cells, they were placed on an immunosuppressive regimen free of glucocorticoids.
Signals of success
The results were striking. Within 90 days, all participants were producing C-peptide, a marker of insulin production, with levels more than doubling by day 365.
Blood sugar control improved in tandem. Before treatment, none had an HbA1c (a long-term measure of blood sugar) below 7%. Four months after the infusion, all did. Their levels stayed below 7% through the year, with an average drop of 1.81 percentage points.
The time each participant spent in the healthy glucose range — 70 to 180 mg/dL — also jumped from about 50% to over 93%. “In the group studied, the response is very encouraging, with clear signs that insulin production and cell function were preserved for a meaningful period of time,” Prof. Thomas said.
Ten participants stopped needing insulin; the other two required far less than before. Each had received high-dose steroids around the time of treatment, in violation of protocol. The authors suggest this may have interfered with cell survival.
The investigators didn’t link either of the two deaths during the trial to zimislecel. One developed cryptococcal meningitis after sinus surgery while on high-dose steroids — against protocol — along with immunosuppressive drugs. The other, who received a half dose and had a prior brain injury from a hypoglycaemia-related accident, died over two years later, from worsening neurocognitive decline.
Other side effects were common but mostly manageable. Participants reported symptoms like headache, diarrhoea, nausea, rashes, and COVID-19 infections. Three developed neutropenia and two experienced acute kidney injury. According to the authors, most of these events were linked to the immunosuppressive drugs, not zimislecel.
A promising start
Phase 3 trials of zimislecel are already underway, with 50 participants from around the world who will be followed for five years. But while long-term data is crucial, the early results are encouraging: the therapy restored insulin production, improved blood sugar control, eliminated severe hypoglycaemic events, and significantly reduced or even eliminated the need for insulin.
That’s no small claim. For decades, researchers have searched for a way to make islet replacement therapies accessible. Zimislecel suggests that large-scale manufacturing may finally make that possible.
In India, where an estimated 1.3 lakh young people are enrolled in the national Young Diabetes Registry and where more than 2.2 million children live with type 1 diabetes, according to global estimates, access to advanced diabetes care remains uneven. While public programmes such as the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke and the Jan Aushadhi scheme aim to improve insulin access and affordability, technologies like continuous glucose monitors and insulin pumps continue to remain out of reach for most.
“This study marks a promising step forward in a field that has seen remarkably slow progress over the last 70 years,” Prof. Thomas said. “But if the therapy is eventually introduced to the market, important questions will remain around its cost and the side-effects related to life-long immunosuppression.”
(Anirban Mukhopadhyay is a geneticist by training and science communicator from Delhi. anirban.genetics@south.du.ac.in)