FDA Approval of Islet Cell Transplant Marks Milestone for UH’s Leading Endocrinologist

Innovations in Diabetes & Metabolic Care | Fall 2024

In 2023, the U.S. Food and Drug Administration (FDA) approved Lantidra™ (donislecel), a breakthrough allogeneic (donor) pancreatic islet cellular therapy for individuals with Type 1 diabetes (T1D).

Betul Hatipoglu, MD

For Betul Hatipoglu, MD, Director of the University Hospitals Diabetes & Metabolic Care Center at Unviersity Hospitals Cleveland Medical Center, Lantidra’s approval marked a momentous professional achievement. Dr. Hatipoglu was among the original researchers who eventually brought islet therapy to the finish line when she served as Medical Director of the Pancreas and Islet Cell Transplant Program at the University of Illinois at Chicago, the only program nationwide currently cleared to offer the novel treatment.

The concept of infusing islet cells from a donor pancreas into the liver of a patient with T1D originated in the 1960s. However, the theory was not initially successful because of the need to provide individuals with effective immunosuppressive drugs to prevent rejection of the insulin-producing cells.

“Immunosuppressive drugs were not that good until the late ’90s, when improvement in these medications led to exciting advances in islet cell therapy as a viable option in the early 2000s,” Dr. Hatipoglu says. “Research starts in academia, but we don’t always get to see projects come to fruition. It is once in a lifetime for many of us.”

An expert on islet cell therapy, Dr. Hatipoglu remained involved with the project after moving to Cleveland. She has been invited to speak internationally on endocrinology and islet cell therapy, including at the World Health Organization and before the FDA.

Lantidra is approved for adults with T1D who experience repeated episodes of severe hypoglycemia despite intensive diabetes management and education. The treatment is delivered via infusion through the hepatic portal vein and requires patients to receive concomitant immunosuppression.

Patients may receive a second infusion if they do not achieve independence from exogenous insulin within one year of infusion or within one year after losing independence from exogenous insulin following a previous infusion. A third infusion may be given following the same criteria used to indicate a second infusion.

The Dangers of Hypoglycemia

“It is estimated that about 20 percent of people with Type 1 diabetes suffer from hypoglycemia unawareness, which can be extremely dangerous and even fatal,” Dr. Hatipoglu says. “Despite the fact that we have amazing diabetic technology today, including insulin pumps, continuous glucose monitors and advanced insulin types, we still have not been able to eliminate this problem.”

A blood sugar level below 54 mg/dL is considered severe hypoglycemia. Falling into a state of unconsciousness is the primary complication of hypoglycemia unawareness, or impaired awareness of hypoglycemia (IAH), which can lead to secondary risks of accidents or severe injury. IAH occurs when an individual does not detect or has a delayed autonomic response to dangerously low glucose levels.

Early results have been remarkable. At one year post-infusion, 100 percent of patients achieved full insulin independence. At five years, 50 to 70 percent of patients remained insulin independent. “The desired outcome is for the patients to be totally insulin-independent and enjoy a close to normal life,” Dr. Hatipoglu says. “However, even if someone goes back to insulin, the severe hypoglycemia episodes seem to improve dramatically.”

More research is needed to improve long-term survival. International studies show that the transplanted islet cells eventually begin to lose their insulin secretory function. “This is true of many transplant therapies — with time, function declines and organs fail,” Dr. Hatipoglu says. “There is an ideal outcome and an acceptable outcome.”

Looking Ahead

As islet therapy begins to expand to additional sites, Dr. Hatipoglu hopes to help more patients with T1D achieve insulin independence. “Currently, donor pancreata are underutilized in the United States, so there is capacity,” she says. “As we equip more centers to safely administer the treatment, we will be able to increase the inclusion criteria and reach a broader population.”

For more information, contact Betul Hatipoglu, MD, at Betul.Hatipoglu@UHhospitals.org.

Contributing Expert:
Betul Hatipoglu, MD
Director
University Hospitals Diabetes & Metabolic Care Center
Vice Chair, UH System Clinical Affairs
Mary B. Lee Chair in Adult Endocrinology
University Hospitals Cleveland Medical Center
Professor
Case Western Reserve University School of Medicine