Four popular diabetes drugs are rapidly gaining critical notoriety in the United States. Januvia (Merck), Janumet (Merck), Byetta (Amylin / Bristol-Myers Squibb) and Victoza (Norvo Nordisk) have been associated with increased risk of pancreatic cancer and thyroid cancer in humans. However, none of the manufacturers of these drugs has seen fit to properly warn the public about these potentially fatal side effects. Consequently, lawsuits have begun springing up around the nation, evidencing a growing public awareness, and a growing number of cancer victims who have taken these drugs.
In August, the Judicial Panel on Multidistrict Litigation established MDL No. 2452 – In Re: Incretin-Based Therapies Products Liability Litigation in Federal District Court for the Southern District of California, the Honorable Anthony J. Battaglia presiding. At the time of its creation, 53 lawsuits were consolidated, with an additional 44 cases expected to be transferred from other jurisdictions. Lawyers in the Mass Torts Section at Beasley Allen are actively involved in this litigation. They continue to review new cases as they come in.
The following is how the incretin-based therapies work. The human body breaks down ingested sugars and starches into glucose, the fuel that gives us energy. Most of this conversion occurs in the liver. Insulin delivers the glucose from the bloodstream into individual cells. Type 2 Diabetes is a disease whereby the body either fails to produce enough insulin to deliver the glucose, or the cells for some reason refuse to receive the insulin. This breakdown in the insulin delivery system causes the blood to accumulate too much glucose (hyperglycemia), which can lead to a myriad of serious and potentially life threatening diabetic complications. The problem can be compounded if the liver produces too much sugar during this process.
Incretin is a natural hormone that prompts the pancreas to release insulin when blood sugar levels are high, such as after we eat. Januvia (sitagliptin), Janumet (sitagliptin combined with Metformin), Byetta (exenatide) and Victoza (liraglutide) are “incretin mimetics.” These drugs “mimic” incretin by prompting the pancreas to release insulin when blood sugar is rising, while at the same time minimizing the pancreatic production of glucagon, the hormone that causes the liver to release its sugar. Ideally, a balance is created between glucose production and glucose consumption.
But stimulating the pancreas to create additional insulin (and to reduce glucagon production) can lead to serious pancreatic inflammation, known as pancreatitis. Acute pancreatitis is defined as a sudden attack causing inflammation of the pancreas, often accompanied by severe abdominal pain. Acute pancreatitis is fatal in approximately 5 percent of cases, and survivors are at increased risk of recurrent pancreatitis or other pancreatic disorders or dysfunction. Chronic pancreatitis is a known risk factor for pancreatic cancer.
Pancreatic cancer has a notoriously poor prognosis for survival. The five-year survival rate is usually estimated around 5 percent. The majority of pancreatic cancer cases occur in people older than age 50. It has few early symptoms or warning signs, often resulting in late-stage diagnosis with few treatment options.
Another troubling observation among the users of incretin-based therapies is an increase in thyroid cancer reports. Early animal studies showed development of thyroid tumors in clinically relevant exenatide and liraglutide exposures. In fact, Victoza now includes a black box warning acknowledging that it causes thyroid C-cell tumors in rodents, and that patients with a family history of thyroid cancer should avoid this drug. While thyroid cancer risk among incretin-therapy users is certainly alarming, most studies have focused more on the pancreatitis/pancreatic cancer threat.
A comprehensive review of the U.S. Food and Drug Administration (FDA) Adverse Event database by researchers at the UCLA School of Medicine and Department of Biomathmatics showed the “use of sitagliptin or exenatide increased the odds ratio for reported pancreatitis six-fold as compared with other therapies. Pancreatic cancer was more commonly reported among patients who took sitagliptin or exenatide as compared with other therapies.” Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1-Based Therapies, Elashoff, et al., Gastroenterology 2011; 141. These five clinical researchers observed the reported event rate for pancreatic cancer to be nearly three times greater in patients taking exenatide and sitagliptin, concluding that their findings “raised caution about the potential long-term actions of these drugs to promote pancreatic cancer.”
A Johns Hopkins study published this year in JAMA Internal Medicine focused on increased incidence of acute pancreatitis in patients taking sitagliptin or exenatide. After studying 1,269 patients hospitalized with acute pancreatitis, as compared to 1,269 diabetic control subjects, these six research physicians concluded even relatively short-term users of these drugs (less than two years) experienced “significantly increased odds of acute pancreatitis relative to the odds in nonusers.” Glucagonlike Peptide 1-Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus, A Population-Based Matched Case-Control Study, Singh, et al., JAMA Intern. Med., Feb. 25, 2013.
Last year, incretin-based treatments for Type 2 Diabetes reached approximately 17 million prescriptions according to IMS Health data. Eleven million (66 percent) of those prescriptions were for sitaglipton. (QuarterWatch, Institute for Safe Medication Practices, April 18, 2013) With the rising popularity of these drugs, we are certain to see a rise in pancreatic and thyroid cancers. Patients considering these drugs should weigh carefully the risks and benefits, and discuss these concerns in depth with their prescribing physician.
For more information about the ongoing litigation in MDL 2452 and related cases, contact David P. Dearing, a lawyer in our firm’s Mass Torts Section, at 800-898-2034 or by email at David.Dearing@BeasleyAllen.com.