--JDRF-funded study shows that a combination of sitagliptin and pantoprazole improves glycemic control in islet transplant recipients with type 1 diabetes who displayed early signs of islet transplant failure--
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New York, NY, June 11, 2012-JDRF-funded researchers at the University of Alberta, Canada have found a way to restore insulin independence in people with type 1 diabetes (T1D) whose blood glucose control had begun to falter after an islet cell transplantation procedure. Presented on Saturday at the American Diabetes Association's (ADA) 72nd Scientific Sessions in Philadelphia, the clinical study showed that a combination therapy of the drugs sitagliptin and pantoprazole successfully boosted transplanted islet cell function in patients with T1D after six months of treatment.
Islet cell transplantation is a rare but useful treatment for T1D in which isolated islets-clusters of cells that produce hormones in the pancreas-are transplanted from a donor pancreas to a person with T1D. The transplanted islets begin to produce insulin and regulate blood glucose, so that the T1D patient may no longer rely on insulin injections to survive, at least for a period of time. For a multitude of possible reasons, not all islet cells survive transplantation, however, leading some islet transplant recipients to experience islet transplant failure, and to thereby resume or increase their insulin usage. Drawing from previous research, the University of Alberta study was designed to determine whether a combination of sitagliptin and pantoprazole could help improve the functioning of transplanted islets in such patients, with the hope of restoring insulin independence.
Sitagliptin, an FDA-approved drug used to treat type 2 diabetes, is an inhibitor of the enzyme called dipeptidyl peptidase-IV (DPP-IV), which breaks down or metabolizes the gastrointestinal hormone incretin (GLP-1). By blocking the degradation of GLP-1, the drug acts to promote the beneficial effects of GLP-1 on beta cell survival and health. Pantoprazole, an FDA-approved drug used to treat gastric acid reflux, has also been shown to promote new beta cell formation in animal models when given at high doses. The precise mechanism by which gastrin exerts this effect on beta cells is not known, but it is thought to promote formation of new beta cells possibly from beta cell precursors in the pancreas.
Based on these observations, Dr. Peter Senior, medical director of the Clinical Islet Transplant Program at the University of Alberta, and his team set out to investigate whether a combination of these drugs could prevent beta cell loss and potentially form new beta cells in a failing islet transplant.
Eight subjects were given the combination therapy of 100 mg of sitagliptin and 40 mg of pantoprazole daily for six months, during which time researchers assessed the patients' blood glucose control and transplant function. The subjects tolerated the study drugs well and did not experience increases in hypoglycemia (extreme low blood sugar). After six months of treatment, five of the eight study participants regained insulin independence. However, their blood glucose control was not maintained beyond three months after the treatment was withdrawn.
The findings show that sitagliptin and pantoprazole can beneficially support the health and function of beta cells in a transplant setting where the beta cell function is deteriorating. The lack of a durable effect after discontinuation of the therapy suggests that the drugs did not promote formation of functional beta cells and/or that any newly formed beta cells will need to be continuously protected from stress conditions in a transplant situation.
"In order for insulin independence to last in islet transplant recipients, the quantity of islet cells appears to be a key determinant," said Albert Hwa, Ph.D., JDRF's senior scientific program manager for cure therapies. "The higher the population of remaining islet cells, the greater the likelihood that insulin independence will continue. Beta cell survival is a key focus of JDRF's research to cure type 1 diabetes, regardless of whether those beta cells are transplanted or a person's own. This research gives us further insight into the potential use of these drugs as part of a cure for type 1 diabetes."
JDRF is also supporting additional clinical research into a similar combination therapy, to determine whether it could improve the survival of beta cells in people newly diagnosed with T1D.
In T1D, a person's pancreas stops producing insulin, a hormone that enables people to get energy from food. People with T1D need to test their blood sugar and give themselves insulin (with injections or an insulin pump) multiple times every day, and carefully balance insulin doses with eating and daily activities throughout the day and night. However, insulin is not a cure for diabetes, and even with that intensive care, a significant portion of the day is still spent with either high or low blood sugar, placing people with T1D at risk for devastating complications such as heart attack, stroke, blindness, and amputation.
JDRF is the leading global organization focused on type 1 diabetes (T1D) research. Driven by passionate, grassroots volunteers connected to children, adolescents, and adults with this disease, JDRF is now the largest charitable supporter of T1D research. The goal of JDRF research is to improve the lives of all people affected by T1D by accelerating progress on the most promising opportunities for curing, better treating, and preventing T1D. JDRF collaborates with a wide spectrum of partners who share this goal.
Since its founding in 1970, JDRF has awarded more than $1.6 billion to diabetes research. Past JDRF efforts have helped to significantly advance the care of people with this disease, and have expanded the critical scientific understanding of T1D. JDRF will not rest until T1D is fully conquered. More than 80 percent of JDRF's expenditures directly support research and research-related education.