Functional Cures for T1D: Insulin Independence Through Islet Transplantation

On June 8, 2026, parent company Eledon Pharmaceuticals announced new updated data from their islet cell transplant trial of tegoprubart in patients with type 1 diabetes. The investigational anti-CD40L antibody allowed all 12 patients to achieve insulin independence and an HbA1c <6.5% while exhibiting no hypoglycemic events post-transplant.¹

Diabetes Dialogue cohosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss tegoprubart and other potential functional cures for type 1 diabetes through islet cell transplantation.

Check out the full episode on potential T1D cures here.

In this segment, Isaacs and Bellini, prompted by increasing discussion on social media and presentations at the American Diabetes Association Scientific Sessions and the AACE Annual Meeting, focus on encouraging early results from an ongoing clinical trial in which all 12 participants have achieved insulin independence following allogeneic islet cell transplantation.

Isaacs explains that the transplanted islet cells restore endogenous insulin production, allowing participants to discontinue insulin therapy while maintaining near-normal glycemic control. She emphasizes that participants have achieved HbA1c values in the 5% range without the restrictive dietary approaches or intensive diabetes management typically required in type 1 diabetes. Several trial participants have also publicly shared their experiences, describing a return to normal eating patterns and sustained euglycemia.

A central focus of the discussion is the novel immunosuppression strategy used in the study. Historically, islet transplantation has required calcineurin inhibitors such as tacrolimus, which are associated with significant toxicities, particularly nephrotoxicity. Isaacs describes the investigational anti-CD40 ligand agent tegoprubart, which was developed to provide effective immunosuppression with a more favorable safety profile. Although the medication is currently administered as an intravenous infusion every three weeks, the hosts note that future subcutaneous or oral formulations could improve long-term feasibility if the therapy reaches broader clinical use.

The hosts also discuss the durability of the response. Participants continue to be followed for up to three years, with several maintaining insulin independence for nearly two years. Bellini describes the finding that all 12 participants achieved insulin independence as particularly noteworthy, especially when compared with earlier islet transplantation efforts such as the Edmonton Protocol, which demonstrated promise but failed to produce similarly consistent outcomes. She characterizes the current findings as among the most encouraging advances she has seen during more than 50 years of living with type 1 diabetes.

Despite the enthusiasm, the conversation also addresses the practical challenges that remain before this approach could become widely available. Bellini highlights the continued dependence on donor pancreatic tissue, emphasizing the importance of increasing awareness around pancreatic donation. She also notes that the trial is currently being conducted at a single center, underscoring the need for larger studies, expanded access, and longer follow-up to confirm the durability of the results. Cost, treatment accessibility, and the long-term burden of chronic immunosuppression are also identified as important considerations for future implementation.

The hosts further explore several intriguing observations from the trial. Two participants required a second islet cell infusion before achieving insulin independence, and both had higher body mass index values, suggesting that greater islet mass may be necessary in individuals with increased insulin resistance. Isaacs also notes that two participants are receiving tirzepatide following transplantation, raising questions about the potential role of adjunctive therapies in optimizing metabolic outcomes after islet replacement.

The episode concludes with a discussion of how these early findings may shape future research. The hosts suggest that patient characteristics such as BMI may eventually inform individualized transplantation strategies, including the amount of transplanted islet tissue required. While emphasizing that important hurdles remain, they agree that these results represent one of the most promising advances toward a functional cure for type 1 diabetes and offer renewed optimism for the future of beta-cell replacement therapy.

Editor’s Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.

References

1. Breakthrough T1D. All 12 Clinical Trial Participants Off External Insulin: New Data on Tegoprubart Continues to Impress. June 7, 2026. Accessed June 29, 2026. https://www.breakthrought1d.org/news-and-updates/tegoprubart-islet-transplant-all-participants-off-external-insulin/