According to the American Diabetes Association, “Type 2 diabetes is the most common form of diabetes. Millions of Americans have been diagnosed with type 2 diabetes…” Type 2 diabetes mellitus is a chronic disease, characterized by insulin resistance and deficient insulin secretion leading to high blood sugar levels or “hyperglycemia,” which is the hallmark of the condition. Diabetes remains the most frequent cause of blindness, amputations and dialysis worldwide. It is considered to be one of the major health challenges of the twenty-first century.
Two of the most recently approved classes of therapeutic agents for the treatment of type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4), are members of a larger class of drugs known as incretin mimetics. Drugs in the incretin mimetic based class of medications, which includes exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto), are supposed to help prevent these diabetic complications.
In February 2010, concerns were published regarding the GLP-1 drugs, including Victoza and Byetta, and the DDP-4 inhibitors, including Januvia and Janumet, and their potential link with pancreatic cancer.
Writing in Diabetes Care, Butler et al. published GLP-1–Based Therapy for Diabetes: What You Do Not Know Can Hurt You’ wherein they wrote, “History has taught us that enthusiasm for new classes of drugs, heavily promoted by the pharmaceutical companies that market them, can obscure the caution that should be exercised when the long-term consequences are unknown. Of perhaps greatest concern in the case of the GLP-1–based drugs, including GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, is preliminary evidence to suggest the potential risks of asymptomatic chronic pancreatitis and, with time, pancreatic cancer.”
In addition, these researchers wrote, “However, in the context of a new class of medical therapy, the proverb ‘What you do not know cannot hurt you’ clearly does not apply. We feel that enough preliminary evidence has accumulated to suggest that there is a plausible risk that long-term recipients of GLP-1–based therapy may develop asymptomatic chronic pancreatitis…, and worse, subsequently a minority of individuals treated by this class of drug may develop pancreatic cancer.”
Further, in February 2011, the journal Gastroenterology published on-line the work of Elashoff et al. titled, Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. These researchers used the FDA Adverse Event Reporting System (FAERS) to assess the association between treatment with Victoza and Januvia and an adverse event report of pancreatitis, where the drugs were listed as the primary suspect associated with a pancreatitis report in the database. A secondary goal was to examine the FAERS database for reported pancreatic or thyroid cancer associated with use of Victoza and Januvia, with various other anti-diabetic drugs used as controls.
These researchers reported, among other things, that the reported event rate for pancreatic cancer was 2.9-fold greater in patients treated with Byetta (and similar drugs in the GLP-1 class, like Victoza) compared to other therapies. The reported event rate for pancreatic cancer was 2.7-fold greater with Januvia (and similar DPP-4 drugs, like Janumet) than other therapies. These researchers noted that the potential to increase the risk of cancer might be expected to occur by “permitting declaration of tumors previously held in check by an intact immune system” as has been published by others within the world’s medical literature.
In April 2012, Public Citizen, a non-profit consumer-advocacy organization based in Washington DC, sent a petition to the FDA to withdraw Victoza (liraglutide), a drug in the GLP-1 class, from the market. Dr. Sidney Wolfe, director of the health and research group at Public Citizen, said at that time, “We don’t just go after drugs casually…(W)e only go after drugs when there is clear evidence of unique dangers or risks, and when there is no evidence of a unique clinical advantage.”
Dr. Wolfe said at the time his concerns extended to other diabetes drugs that alter the GLP-1 pathway, which would now include the entire incretin mimetic based class of medications: exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). The petition to withdraw Victoza was based on information pulled from the FDA’s adverse-event reporting database. Public Citizen counted 28 cases of pancreatic cancer reported between February 2010 and September 2011 among patients on Victoza, compared with just one case in a patient taking a diabetes drug that does not manipulate the GLP-1 pathway.
Unfortunately for patients, the evidence against these drugs has continued to mount. On March 22 2013, in an on-line publication within the journal Diabetes, Butler et al published the results of their examinations of the pancreata obtained from organ donors with and without diabetes treated by incretin-based therapies (> 1 yr) or other therapy and non diabetic controls. These researchers observed that pancreatic mass was increased in diabetes patients treated with incretin-based therapies compared to that in individuals with diabetes not treated with such agents, and that the increase was statistically significant. They also observed that the pancreatic fractional insulin area was reduced in diabetics patients not treated with incretin-based therapies compared to non-diabetic controls, again, a statistically significant result. In contrast, they observed that the pancreatic fractional insulin area was approximately 5-fold increased in diabetic patients treated with incretin-based therapies when compared to individuals not treated with incretin-based therapies, also statistically significant. These researchers noted that the increased pancreatic mass in diabetics induced by incretin-based therapies was accompanied by increased whole pancreas cell and an increase in the presence of pancreatic intraepithelial neoplasia (PanINs), both observations being statistically significant.
These observations by Butler et al that the pancreatic mass of the individuals with diabetes treated with incretin-based therapies was increased in comparison to diabetics not treated with incretin-based therapies is consistent with prior rodent studies that revealed proliferative actions of GLP-1 on the exocrine pancreas – extending the animal studies to human studies.
A striking finding in the studies by Butler et al is the marked expansion of the exocrine and endocrine compartments of the pancreas with incretin-based therapies. The findings of an increased pancreatic mass, increased PanIN lesions, and endocrine proliferations by Butler et al in response to GLP-1 mimetic therapy adds significantly to concerns already shown regarding the adverse actions of GLP-1 mimetic therapy to induce pancreatitis and accelerate pancreatic dysplasia. Prior reports concerning pancreas changes with incretin-based therapy were generally confined to studies of rodent pancreas, but have since been unquestionably extended by Butler et al to humans with the added concern of developing neuroendocrine tumors.
Sadly, due to the flawed formulation of these drugs, we believe incretin-based therapies like Januvia, Byetta, Janumet and Victoza increase the risk of pancreatic cancer in those diabetic patients to whom they are prescribed. Unfortunately, the manufacturers of these drugs have failed to even mention ‘pancreatic cancer’ in their respective product inserts or warning labels – placing patients ingesting these drugs at risk of developing deadly pancreatic cancer. We believe these companies should be accountable for their actions, and as a result, we have filed numerous lawsuits against them in state and federal courts across the country.
Firm partner, Ryan Thompson, was appointed to serve as Co-Lead counsel nationally in the Incretin-Based Therapies MDL by US District Judge Anthony Battaglia for plaintiff’s who developed pancreatic cancer as a result of ingesting Byetta, Januvia, Janumet, and or Victoza.
Written by:
Ryan L. Thompson
Watts Guerra LLP
4 Dominion Drive, Bldg. 3, Suite 100
San Antonio, Texas 78257
Phone (210) 447-0500
Email rthompson@guerrallp.com
*This information is provided to supply information relating to claims of pancreatic cancer associated with ingestion of incretin-based therapies and should not be received as legal advice. Legal advice is only given to persons or entities with whom Watts Guerra LLP has established an attorney-client relationship. If you have a lawyer, you should consult with your own attorney.
© Watts Guerra LLP 2015
