Efficacy and Safety of Allogeneic Islet Transplantation Demonstrated by a Multicenter Clinical Trial in Japan.

Background: Islet transplantation in type 1 diabetes mellitus restores endogenous insulin secretion and hypoglycemia awareness. Although high-quality prospective clinical trials have demonstrated the efficacy of islet transplantation, reports on the clinical outcomes in Asia remain scarce. Therefore, we conducted a clinical trial in Japan to verify the effectiveness of islet transplantation. Methods: This multicenter, single-arm study aimed to evaluate the clinical efficacy and safety of immunosuppressive therapy for allogeneic islet transplantation. The immunosuppressive regimens included antithymocyte globulin, calcineurin inhibitors, and mycophenolate mofetil. The primary endpoint was a glycated hemoglobin level of <7.4% on day 365 and the absence of severe hypoglycemic events from 1 mo to 1 y after the first transplantation. Results: Eight recipients with evaluation data obtained 1 y after the initial transplantation were included in the efficacy analysis. Of the 8 recipients, 3, 3, and 2 recipients received 1, 2, and 3 islet infusions, respectively. Six recipients (75%) achieved the primary endpoint. The median glycated hemoglobin levels declined from an initial 7.3% to 6.3% and 6.1% on days 375 and 730, respectively, with related improvements in hypoglycemia awareness and glucose variability. No complications associated with intraportal transplantation, such as intraperitoneal hemorrhage or portal vein embolism, were observed. Conclusions: Islet transplantation provided near-normal glycemic control and protection against severe hypoglycemic events in patients with type 1 diabetes mellitus in this Japanese cohort. Future studies are needed to confirm whether long-term graft survival can be achieved and whether it is possible to prevent the progression of diabetic complications.