New Immunosuppression Approach Shows Promise in Islet Transplant Study

Islet transplantation—transferring insulin-producing cells from a donor pancreas into a person with Type 1 diabetes—can restore the body's ability to regulate blood sugar. For people with severe hypoglycemia unawareness, who cannot detect dangerously low blood sugar, this procedure can be life-changing.

The challenge is that transplanted islets are recognized as foreign by the immune system. To prevent rejection, transplant recipients must take immunosuppressive drugs for life. Current standard therapy relies on calcineurin inhibitors like tacrolimus, which work well but can harm the kidneys over time and cause other side effects. Researchers have been searching for alternatives that could work as well or better with fewer complications.

This international clinical trial examined whether two drugs used successfully in other organ transplants could improve outcomes in islet transplantation. The new combination was belatacept, a co-stimulatory blocker that prevents immune cells from attacking the transplant, paired with sirolimus, a mammalian target of rapamycin inhibitor that also suppresses immune response.

Nine participants received the new belatacept and sirolimus combination, while 24 received the standard tacrolimus and mycophenolate mofetil regimen. Researchers tracked whether people achieved freedom from hypoglycemic episodes, positive C-peptide (a marker of islet function), and good blood sugar control (HbA1c below 53 mmol/mol or 7.0%) at 12 months.

Eight of nine participants (89%) on the new belatacept and sirolimus combination met the primary outcome of freedom from hypoglycemia with preserved islet function and controlled blood sugar. In comparison, 12 of 24 participants (52%) on the standard regimen achieved this same outcome.

Both groups showed improvements in HbA1c, blood sugar control, and reduced insulin requirements. However, only the belatacept and sirolimus group maintained stable kidney function throughout the study. In the standard tacrolimus group, some participants experienced measurable changes in kidney function, a known concern with calcineurin inhibitors.

The study also examined immune responses in both groups to understand how well each drug combination controlled unwanted immune activity against the transplanted islets.

This was a phase 2, non-randomized, open-label trial—an early-stage design used to gather preliminary evidence. The small number of participants (33 total) means results should be interpreted as promising signals rather than definitive proof. Both groups were treated at the same time but not randomly assigned, which introduces potential bias.

Larger, randomized controlled trials comparing these immunosuppression strategies are needed to confirm whether belatacept and sirolimus truly outperform standard therapy and remain safe over many years. Additional research must also explore long-term kidney protection, durability of islet function, and quality of life for transplant recipients on each regimen.

Islet transplantation remains a specialized procedure available only to carefully selected patients with Type 1 diabetes and severe hypoglycemia unawareness. Anyone considering transplantation should discuss all options, risks, and expected outcomes with their transplant team.

Source: Diabetologia. Evidence type: PubMed indexed literature. Type1Cure is an information and intelligence hub, not a medical advice service. This article summarizes published research and does not provide diagnosis, treatment, or personal medical guidance. Always talk to your own care team before changing anything about your Type 1 diabetes management.