Despite advances in blood glucose monitoring and insulin delivery, most people living with type 1 diabetes do not meet their glycemic targets. Beta-cell replacement therapy may help address this gap in care.

In the Joint ADA/IPITA Symposium—Clinical Beta-Cell Replacement Therapy Today, held on Friday, June 21, experts discussed the potential benefits of beta-cell replacement therapy for patients with type 1 diabetes. The symposium can be viewed on-demand by registered meeting participants on the virtual meeting platform. If you haven’t registered for the 84^th Scientific Sessions, register today to access the valuable meeting content through Aug. 26.

“With whole pancreas transplants, we’re able to restore endogenous insulin production such that people are able to come off of insulin and have normal glucose tolerance,” said Anna Lam, MD, MSc, University of Alberta, Canada. With islet transplantation, patients are protected from hypoglycemia even as islet graft function declines.

Dr. Lam discussed how patient evaluation for beta-cell replacement therapy should include a careful, case-by-case assessment of metabolic complications, suitability for transplant procedures, and immunosuppression. Indications include having type 1 diabetes for more than five years, age 18-65, low/undetectable C-peptide levels, and problematic hypoglycemia.

Typically, pancreas transplantations are for younger patients seeking insulin independence, while islet transplantations are for older patients aiming to stabilize blood glucose and prevent hypoglycemia.

Jane Speight, MSc, PhD, CPsychol, FBPsS, Deakin University, discussed the psychological impact of islet and pancreas transplantation. From a systematic review, she found that islet transplantation reduced fear of hypoglycemia and improved quality of life. In contrast, islet and pancreas transplantation had mixed effects on general health and mood.

“The full impact and experience of these types of transplants are still somewhat unclear in terms of the perspective of the people who are undertaking the transplants,” she said.

To better understand this, Dr. Speight analyzed the impact of islet transplantation on quality of life using novel, rigorously designed measures that enabled more comprehensive patient evaluation. While the sample size was too small for statistical analysis, the study found that patient quality of life generally improved after islet transplantation.

Michiel Nijhoff, MD, MSc, Einthoven Laboratory, the Netherlands, discussed monitoring and treating rejection or type 1 diabetes recurrence in patients receiving beta-cell replacement therapy.

“You can wonder when the patient has acute graft failure, is this recurrence or rejection?” Dr. Nijhoff said. “Well, that’s quite difficult, and that’s because the pathophysiology is quite similar.”

However, acute graft failure is prevalent, with an incidence of 20­–25 percent versus 2.5 percent for recurrence of type 1 diabetes.

Clinicians should be alert for signs of rejection, including pancreatitis, hyperglycemia, and immune activation, Dr. Nijhoff said. It is critical to diagnose rejection or recurrence of type one diabetes early, as they are both associated with poor outcomes. However, if treated early and appropriately, graft damage can be mitigated.

Piotr Witkowski, MD, PhD, University of Chicago, presented updated data from the phase 1/2 FORWARD study of VX-880 in participants with type 1 diabetes, impaired awareness of hypoglycemia, and severe hypoglycemia. VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy.

Participants receiving a full dose of VX-880 demonstrated islet cell engraftment with clinically meaningful endogenous insulin production and improved glucose control by day 90, Dr. Witkowski said. All three participants with greater than a year of follow-up met the primary endpoint and were free of severe hypoglycemic events with improved glucose control.

The safety profile of VX-880 was consistent with the immunosuppressive regimen, infusion procedure, and long-standing type 1 diabetes.