FDA approves Tanzeum to treat type 2 diabetes

FDA approves Tanzeum to treat type 2 diabetes

The U.S. Food and Drug Administration today approved Tanzeum (albiglutide) subcutaneous injection to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes.

Type 2 diabetes affects approximately 24 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.

"Tanzeum is a new treatment option for the millions of Americans living with type 2 diabetes," said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA's Center for Drug Evaluation and Research. "It can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of diabetes."

Tanzeum is a glucagon-like peptide-1 (GLP-1) receptor agonist, a hormone that helps normalize blood sugar levels. The drug's safety and effectiveness were evaluated in eight clinical trials involving more than 2,000 patients with type 2 diabetes. Patients participating in the trials showed an improvement in their HbA1c level (hemoglobin A1c or glycosylated hemoglobin, a measure of blood sugar control).

Tanzeum has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies, including metformin, glimepiride, pioglitazone, and insulin. Tanzeum should not be used to treat people with type 1 diabetes; those who have increased ketones in their blood or urine (diabetic ketoacidosis); or as first-line therapy for patients who can't be managed with diet and exercise.

Tanzeum has a Boxed Warning to warn that tumors of the thyroid gland (thyroid C-cell tumors) have been observed in rodent studies with some GLP-1 receptor agonists, but that it is unknown whether Tanzeum causes thyroid C-cell tumors, including a type of thyroid cancer called medullary thyroid carcinoma (MTC), in humans. Tanzeum should not be used in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (a disease where patients have tumors in more than one gland in their body and that predisposes them to MTC).

The FDA is requiring the following post-marketing studies for Tanzeum:

a clinical trial to evaluate dosing, efficacy, and safety in pediatric patients;

a medullary thyroid carcinoma (MTC) case registry of at least 15 years duration to identify any increase in MTC incidence related to Tanzeum;

a cardiovascular outcomes trial (CVOT) to evaluate the cardiovascular risk of Tanzeum in patients with high baseline risk of cardiovascular disease.

In clinical trials, the most common side effects observed in patients treated with Tanzeum were diarrhea, nausea, and injection site reactions.

The FDA approved Tanzeum with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care providers about the serious risks associated with Tanzeum.

Tanzeum is manufactured by GlaxoSmithKline, L.L.C., Wilmington, Del.

http://www.medicalnewstoday.com/releases/275644.php

Featured Research

from universities, journals, and other organizations

Factor present in gestational, type 2 diabetes could provide new treatment options

New research reveals that both pregnant women with diabetes and with type 2 diabetics have high levels of a fat metabolite that impairs pancreatic cells from secreting insulin. The findings, which are published in the April 1 issue of the Cell Press journal Cell Metabolism, suggest that blocking the effects of this fat metabolite may help prevent and treat diabetes.

In nearly one-fifth of pregnancies, diabetes can arise (called gestational diabetes), and when this happens, it puts the woman at an increased risk for developing type 2 diabetes later in life. To gain better insights into the shared mechanisms behind these two types of diabetes, researchers in Dr. Michael Wheeler's lab at the University of Toronto examined more than 340 molecules in blood samples from individuals with gestational diabetes, individuals with type 2 diabetes, and individuals without diabetes. The researchers used a metabolomics approach, which involves the study of chemical processes involving metabolites.

The team found that the blood of both gestational and type 2 diabetic patients contained a remarkable number of changed metabolites, including sugars, amino acids, and fats, compared with samples from nondiabetic controls. One particular fat metabolite, called CMPF, was dramatically increased in both gestational and type 2 diabetic individuals compared to those without diabetes. Experiments in mice showed that this increased concentration of CMPF caused a decrease in insulin secretion from beta cells in the pancreas, which led to the development of diabetes.

More detailed mechanistic experiments revealed that CMPF enters a beta cell through what's called organic anion transporter 3 (OAT3), and once inside the cell it causes oxidative stress and other negative effects. Next, the researchers found that the effects of CMPF could be prevented through either blocking the transport of CMPF into insulin-producing beta cells or treatment with antioxidants.

"Based on our findings we believe that CMPF and its transporter OAT3 represent novel targets for prevention and treatment of diabetes," says first author Kacey Prentice. "If we can reduce levels of CMPF in the blood, or prevent CMPF from entering the beta cell through blockage of OAT3, we believe that we can preserve beta cell function and prevent the beta cell failure that ultimately causes diabetes."

According to Prentice, it is important to note that the treatment of gestational diabetes is a very sensitive topic due to potential risks to both the mother and the developing fetus. "Due to this, we believe the prevention and treatment of type 2 diabetes is a more realistic and widely acceptable goal; however, CMPF has great potential for use as a biomarker of both conditions."

http://www.sciencedaily.com/releases/2014/04/140401122359.htm

Autoimmune drug may help prevent kidney disease caused by diabetes

A drug currently used to treat autoimmune disease may also help prevent the kidney-damaging effects of diabetes, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest that clinical trials should be designed to test the drug in diabetic patients.

Kidney disease is one of the most serious complications of diabetes. Diabetics who develop kidney disease, or diabetic nephropathy, due to high blood glucose levels may eventually require dialysis or a kidney transplant.

Paolo Fiorina, MD, PhD (Boston Children's Hospital/Harvard Medical School) and his colleagues have discovered that a receptor called B7-1 is expressed by kidney cells during the progression of diabetic nephropathy. Furthermore, targeting this receptor with an available drug called CTLA4-Ig, or abatacept, helped to maintain kidney function in mice with diabetic nephropathy. Abatacept is currently being used to treat autoimmune disease due to its ability to target B7-1 expressed on immune cells.

"The next steps will be to test anti-B7-1 drugs in individuals with diabetes and diabetic nephropathy to see if they can abrogate the progression of the disease in humans as well," said Dr. Fiorina.

http://www.sciencedaily.com/releases/2014/03/140327222206.htm

How rotavirus infection accelerates autoimmune diabetes in a mouse model

A combination of genetic predisposition and environmental factors is believed to cause autoimmune (type 1) diabetes. A study published on March 27th in PLOS Pathogens gets at the mechanisms by which rotavirus infection contributes to autoimmune diabetes in a mouse model of the disease.

NOD (for non-obese diabetic) mice are prone to develop diabetes, and infection with rotavirus accelerates onset of the disease. Barbara Coulson and colleagues, from The University of Melbourne, Australia, tested the hypothesis that the virus does this by inducing "bystander activation."

Bystander activation assumes that a foreign intruder (in this case rotavirus) provokes a strong but non-specific activation of the immune system, and that this heightened state of activation "spills over" to a subset of specific immune cells that can recognize and attack not the viral intruder but some of the body's own cells, in this case the insulin-producing islet cells in the pancreas.

Indeed, the researchers found that when spleen cells from NOD mice encounter rotavirus, they activate two types of immune cells: antibody-producing B cells and so-called dendritic cells that are a key part of a coordinated immune response. They could show that this activation involves "unpacking" of the virus (thereby exposing its viral immune activators), as well as specific immune mediators of the host, including one called TLR7 and type 1 interferons.

Rotavirus activation of a specific dendritic cell type called plasmacytoid dendritic cells was necessary for activation of another type of immune cells called T cells. These T cells can recognize and destroy islet cells and are ultimately responsible for type 1 diabetes. When activated, plasmacytoid dendritic cells produce very high levels of type 1 interferons, suggesting it has a specific role in mediating the bystander

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