A Less Toxic Path to Insulin Independence: Inside the Tegoprubart Islet Transplant Trial
For people living with "brittle" type 1 diabetes, the kind marked by frequent, unpredictable, and dangerous low blood sugar episodes, islet transplantation has long held promise as a way to restore the body's own ability to make insulin. But the treatment has always come with a catch: the immunosuppressive drugs needed to protect the transplanted cells from rejection are often just as hard on the body as the disease they're meant to treat.
A small but closely watched trial at the University of Chicago Medicine is testing whether that trade-off is finally changing.
The Problem With Standard Immunosuppression
Islet transplantation works by isolating insulin-producing islet cells from a deceased donor's pancreas and infusing them into a recipient's liver through a small catheter, where they lodge in tiny blood vessels and begin producing insulin. It's a minimally invasive procedure, and when successful, it can let people stop injecting insulin altogether.
The problem is what comes after. Because the transplanted islets come from another person, the recipient's immune system will attack them as foreign material unless it's suppressed. The standard drug for this job, tacrolimus, is a calcineurin inhibitor, and calcineurin inhibitors are notoriously hard on the body. They're linked to kidney toxicity, high blood pressure, and neurological side effects. Worse, in the context of an islet transplant, they can directly damage the very insulin-producing cells they're supposed to be protecting, undermining the whole point of the procedure.
A New Approach: Tegoprubart
That's where tegoprubart comes in. Developed by Eledon Pharmaceuticals, tegoprubart is a monoclonal antibody that targets CD40 ligand (CD40L), a protein central to activating the immune response. Rather than broadly suppressing immune function the way calcineurin inhibitors do, it's designed to dampen the specific signaling pathway that would otherwise trigger rejection, theoretically offering effective protection against rejection without the same collateral damage.
Who Qualifies
This isn't a trial for anyone with type 1 diabetes. It targets a specific, high-risk group. To enroll, participants had to be:
Adults between 18 and 65 years old
Living with type 1 diabetes for at least 5 years, with onset before age 40
Under active, intensive management by an endocrinologist, with quarterly evaluations in the year before screening
Using an insulin pump, multiple daily injections, or continuous glucose monitoring
Still experiencing at least three unexplained severe hypoglycemic events in the prior 12 months, despite that level of care
In other words, these are people doing everything right and still facing dangerous, unpredictable blood sugar crashes, the population islet transplantation was designed to help in the first place. The trial's participants had a median disease duration of about 33 years and an average HbA1c of roughly 8.0% before transplant.
The Results So Far
The trial is small, a pilot study of 12 adults, but the results presented at the American Diabetes Association's 86th Scientific Sessions in June 2026 were striking:
All 12 participants achieved insulin independence, meaning they no longer need external insulin therapy at all.
HbA1c came in below 6.5% for every patient, a dramatic improvement from the roughly 8.0% baseline, and within a near-normal range.
Islet graft function has remained stable across the cohort, with a median follow-up of 8 months and a maximum of 22 months.
Eledon has reported no evidence of the toxicities typically associated with calcineurin inhibitors like tacrolimus.
Earlier readouts told a consistent story. In preliminary data from the first six patients, reported in late 2025, all evaluable participants remained insulin-free, with the drug generally well tolerated and no serious infections, thromboembolic events, rejection episodes, or signs of kidney or neurological toxicity.
Why It Matters, and Why to Stay Cautious
The appeal here isn't just "another islet transplant trial." It's the possibility of decoupling the benefits of islet transplantation from the toxic baggage of its immunosuppression regimen, potentially making the procedure safer, more durable, and eventually more accessible to more patients.
That said, it's worth keeping the results in perspective:
This is a small, non-randomized pilot study: 12 patients, no control group. It's an encouraging early signal, not proof at scale.
It doesn't solve the donor supply problem. The trial uses islets from deceased donors, and donor tissue remains a limiting factor for how many people could ever access this kind of treatment.
It's not a cure. Patients still require lifelong immunosuppression, just, so far, a less damaging version of it.
Eligibility remains narrow, restricted to those with severe, hard-to-control disease and recurrent severe hypoglycemia, similar to who qualifies for islet transplants today.
Eledon has said it's in discussions about a potential path to market for tegoprubart in islet cell transplantation. For now, the tegoprubart islet trial stands as a small but genuinely promising step. It's not a cure for type 1 diabetes, but it's a meaningful attempt to make one of its most effective existing treatments substantially safer.