What are Incretin Mimetics?
Incretin is a natural hormone that is produced by the body. It tells the body to release insulin, which lowers blood sugar after eating. Incretin mimetics are a class of Type-2 diabetes medications that act like, or mimic, the incretins in the body that lower blood sugar after eating.
There are two categories of incretin mimetics. One works by mimicking a hormone called GLP-1 to stimulate natural insulin production. The other is known as a DDP-4 inhibitor and it works by inhibiting glucagon release thereby stimulating insulin secretion.
- GLP-1’s – Byetta, Victoza, Byuderon
- DDP-4’s – Onlgyza, Kombiglyze XR, Januvia, Nesina, Tradjenta, Janumet
In 2007, the FDA warned that incretin mimetics may cause pancreatic diseases. The warning was based on reports that an increased number of users of incretin mimetics were diagnosed with acute pancreatitis and pancreatic cancer. From 2006 to 2009 alone, 88 cases of acute pancreatitis were linked to Januvia. Half of these patients indicated that pancreatic inflammation diminished after they stopped taking Januvia.
Januvia and Janumet are manufactured by Merck, Byetta is manufactured by Amylin Pharmaceuticals, Inc. and was at one point co-promoted by Eli Lilly, & Co., and Victoza by Novo Nordisk. Onglyza and Kombiglyze XR are both manufactured by AstraZeneca and Bristol Myers Squibb.
In the United States, more than 3 million diabetics took the top five selling incretins in 2013, according to estimates from the Institute for Safe Medication Practices.
The drugs are top sellers for the manufacturers, causing concern that the companies do not care about the well-being of the individuals taking the drugs, but, care instead of the profits the drugs bring in.
Study Indicates Type-2 Diabetes Drugs Carry Extreme Risk of Pancreatic Complications
Studies of the effects of incretin mimetics are crucial to understanding how these drugs may be affecting consumers in adverse ways. Consumers rely on this information to make educated decisions when choosing medications.
Researchers who were not wholeheartedly convinced by the supposed safety of incretin mimetics decided to look to the FDA adverse reporting system to see how these drugs affected humans. In individuals who took incretin mimetics, the researchers found an increase in the number of reports of pancreatitis and pancreatic cancer.
Yet, it was not just researchers who noted the link. In September 2008, drug manufacturer Eli Lilly noticed a connection between Byetta and pancreatitis. However, they maintained that the warning on the drug of contracting acute pancreatitis was sufficient and adequately communicated. Furthermore, in 2009, the FDA asked Merck and other companies that manufactured these drugs to do further safety studies using rats which resulted in the death of three rats. Frighteningly enough, the pharmaceutical companies continue to state that these drugs cause no damaging effects.
In an independent analysis of health insurance published in February 2013, researchers found that people taking GLP-1 incretin mimetics were at twice the risk of hospital admission for acute pancreatitis as compared with people taking other anti-diabetic drugs.
In 2013, an independent body released the results of its research indicating that the entire class of incretin mimetics may carry up to 20 times the risk of developing pancreatic cancer for patients taking these drugs.
The Institute for Safe Medication Practices “ISMP” analyzed data from the FDA Adverse Event Reports between July 1, 2011, and June 30, 2012, from 1,723 patients taking these drugs. The ISMP concluded that the increased risk of developing pancreatic cancer for patients taking these drugs could be as much as 20% higher than those who were taking other medications to control their type-2 diabetes.
Tom Moore, a senior scientist for drug safety and policy at the ISMP said, “I think the whole class is in question.” Moore further stated that additional analysis is required, but “if the results are confirmed in a broader patient population, it raises questions about the entire class of drugs.”
Although this data has some inherent limitations because it is based on adverse event reporting, it is a significant signal that more study and investigation should be undertaken, especially considering the other reports from different investigators found similar alarming connections between the drugs and pancreatic cancer.
The results of these studies are very unfavorable to the drug manufacturers who continue to maintain that their product is safe. Unsurprisingly, this research has shown that these manufacturers continue to put profit above safety when they conduct inadequate testing and put unsafe drugs on the market.
In an effort to dismiss allegations that their product was unsafe, Merck offered to fund a professor at the University of California, Los Angeles to conduct a study about the effect of sitagliptin (Januvia) on rats that have diabetes similar to that in humans. What should not have been a shock to Merck, the results of this study demonstrated that their product caused an increase in pancreatic damage.
During the 12-week study, the researchers gave the rats sitagliptin, metformin, or a combination of both drugs. When examining the rats after the 12 weeks, the researchers found that every rat given sitagliptin had an enlarged pancreas. Furthermore, one rat showed acute pancreatitis and 3 out of 16 had acinar to ductal metaplasia, a pathological change thought to be a potential precursor of pancreatic cancer. Immediately after these results were published, Merck held a closed-door meeting to discuss the adverse findings. In this meeting, a professor of digestive diseases said that the results of the study could suggest an increased risk of pancreatic cancer. Had Merck and other pharmaceutical companies adequately tested these drugs before rushing them to the market, they likely would have found these results before the drug caused pancreatic damage to thousands of users.
Is there an Incretin Mimetics Lawsuit?
Plaintiffs and their families throughout the United States have alleged that they now suffer or have died from pancreatic cancer as a result of taking these types of drugs.
In August 2013, a panel of federal judges entered an order consolidating all current and future Byetta, Januvia, Janumet, and Victoza cases into one courtroom in the Southern District of California under the title In re:Incretin Mimetics-Based Therapies Products Liability Litigation due to the increasing number of lawsuits against manufacturers.
Given the complexity of this litigation and anticipated resource demands that accompany “mass tort” (multiple plaintiffs injured in a similar fashion by a defective product) cases, the consolidation is intended to allow the litigation to move forward in an efficient, organized and timely manner. The consolidation of these mass tort cases is called multidistrict litigation, or an MDL.
These actions involved a common question of fact making multidistrict litigation an efficient option for the courts to promote the just and efficient conduct of this litigation. Despite the fact that the courts are generally hesitant to create an MDL for multiple defendants, the panel of judges proceeded with centralization with the support of the defendants – Merck, Amylin, Eli Lily, AstraZeneca, Bristol Myers Squibb, and Novo Nordisk.
As the case proceeded, the defendants argued that the plaintiffs in the MDL had no claim to a “failure to warn” incretin lawsuit, citing the FDA’s approval of the drugs’ labels. In ruling on the summary judgment motion, the trial judge agreed with the defendants and dismissed 749 pending cases.
In September 2016, the plaintiffs’ attorneys filed an appeal to the summary judgment decision with the 9th Circuit U.S. Court of Appeals.
In December 2017, the appellate court returned a decision, determining that the district court had misapplied a Supreme Court case, Buckman Co. v Plaintiffs’ Legal Committee, 531 U.S. 341 (2001), in two ways: (1) the district court relied on Buckman to impermissibly circumscribe discovery, and (2) the district court relied on Buckman to deem the plaintiffs’ newly discovered evidence “irrelevant” to the court’s preemption analysis at the summary judgment stage. Either of these errors, independently, would have warranted a reversal on the dismissal decision.
The court’s opinion further holds that the court abused its discretion in partially excluding plaintiffs’ expert, Dr. Fleming.
Now, the 749 previously dismissed cases, along with new cases that have joined MDL 2452 since the original dismissal, will continue on towards trial in the Southern District of California.
The individuals involved in MDL 2452 claim that the “defendants willfully, wantonly, and with malice withheld the knowledge of an increased risk of pancreatic cancer in users of the Drugs to prevent any chances of their products’ registration being delayed or rejected by [the] FDA.”
The Complaint further alleges that (1) the defendants manufactured defective drugs which caused “unreasonable and dangerous side effects,” (2) the defendants failed to conduct adequate research and test the incretin mimetic drugs before making them available on the market, (3) the defendants failed to warn healthcare professionals and consumers of these potential side effects, even concealing the risks of pancreatitis and pancreatic cancer from the public (4) the manufacturers failed to include specific wordage, such as “pancreatic cancer”, on the drugs’ labels, and (5) the plaintiffs allege that the current warnings for the drugs are still inadequate.
MDL 2452 proceedings resumed after the 9th Circuit issues its mandate — the formal order transferring cases back to the district court. Generally, the mandate is issued 21 days after the release of the opinion, but the release can be pushed back if the defendant’s petition for rehearing within the 14-day filing window. If a rehearing is denied, the mandate will issue sometime around 7 days after the court denies rehearing.
The defendants also had 90 days to file a petition for certiorari at the Supreme Court level. If the defendant’s petition for rehearing, then the deadline for a cert petition is pushed back to 90 days after the denial of rehearing.
FDA Approval System Growing Concern
As pharmaceutical drug liability cases continue to grow, many are left questioning the FDA’s approval method of these dangerous drugs. FDA approval is based on surrogate measures, such as tests that lower blood sugar levels but not on proof that they prevent heart attacks. Drugs can be approved so long as they are deemed safe in early studies based on the limited surrogate measures.
FDA’s Adverse Events Reporting System collects case reports from the public and medical community. Nevertheless, the majority of cases are unaccounted because the reporting system is voluntary for users and health professionals. Although drug companies are required to file reports, patients and doctors rarely report incidents to drug manufacturers. The system is deeply flawed as there are more reports that staff can review, thus it may be years after a drug was approved before the public is warned of any side effects.
According to an analysis of case reports from 2004 to March 2014, there were 964 deaths and 4425 hospitalizations amongst users of Januvia. The analysis also reported 880 deaths and 7115 hospitalizations amongst users of Byetta.
The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are continuing to investigate the connection between this class of drugs and pancreatic cancer.
Why are Incretin Mimetics Still on the Market?
More concerning news surrounding popular Type-2 diabetes medications and their link to pancreatic cancer has come to light. Independent academic and scientific researchers have called on the FDA to take a serious look at their data concerning certain incretin mimetics and their potential to cause this serious and oftentimes fatal form of cancer.
At the urging of these researchers, the FDA is currently reviewing a recent body of research that suggests pre-cancerous cellular changes in the body may be triggered by incretin mimetic medications. These changes may produce an inflammation of the pancreas, which has been shown to cause pancreatic cancer.
In addition, reports of pancreatitis associated with the use of these drugs continue to flood through the doors of the FDA.
As of 2019, both classes of incretin mimetics are still being marketed to millions of people with Type-2 diabetes. But, there is a reason for the manufacturer’s insistence the drugs are safe for consumers. Merck’s global sales increased from $2.39 billion in 2010 to $3.7 billion in 2017. Additionally, the manufacturer has since released newer Type-2 diabetes medications, likely to be profit-driving drugs, too.
More and more research continues to emerge linking these Type-2 diabetes medications with pancreatic cancer, pancreatitis, and thyroid cancer. However, the profits of incretin mimetic drugs are substantial. Manufacturers are not going to give up these products without a fight.
Interested in an Incretin Mimetics Lawsuit? TorHoerman Law Can Help
If you or a loved one have suffered side effects such as pancreatitis or pancreatic cancer that is believed to be caused by Byetta, Victoza, Byuderon, Onglyza, Kombiglyze XR, Januvia, NEsina, Tradjenta, or Janumet, contact TorHoerman Lawto review your legal options in an incretin mimetics lawsuit.