Incretin mimetics, a class of Type 2 diabetes drugs, are sparking debate and renewing concerns about health risks, especially to the pancreas. In fact, a piece published in the journal BMJ, states that the drugs, which include Byetta and Januvia, might be riskier than initially believed.
According to the journal,drug companies have withheld data on the potentially dangerous effects of incretin mimetics. BMJ analyzed thousands of pages of regulatory documents it obtained under Freedom of Information rules, locating unpublished data indicating, “unwanted proliferative or inflammatory pancreatic effects,” according to MedPage Today. “On their own, the individual pieces of unpublished evidence may seem inconclusive, but when considered alongside other emerging and long-standing evidence, a worrying picture emerges, posing serious questions about the safety of this class of drug,” Deborah Cohen, Investigative Editor for BMJ, wrote.
Incretin mimetics include Byetta and Bydureon (exenatide); Victoza (liraglutide); Januvia, Janumet, Janumet XR, and Juvisync (sitagliptin); Onglyza and Kombiglyze XR (saxagliptin); Nesina, Kazano, and Oseni (alogliptin); and Tradjenta and Jentadueto (linagliptin). The drugs increase natural substances that lower raised blood sugar levels. Typically, patients with Type 2 diabetes are either diagnosed with abnormally low insulin levels or their bodies do not utilize insulin efficiently. The drugs imitate the body’s incretin hormones, which stimulate insulin release after consuming a meal.
In her report, Cohen indicated that drug makers have not conducted critical safety studies. What’s more, regulators have not requested such studies, according to MedPage Today. She also noted that access has been denied to the raw data that would have shed light on the safety of incretin mimetics.
The piece presents what MedPage Today describes as a “thorough timeline of incretin mimetic-related events,” that begins with the early signs of pancreatic risk seen in the drug class, which was the brought to the attention of United States and European regulators; boxed warnings discussing pancreatitis; and UCLA’s Peter Butler, MD’s work exposing risks associated with incretin mimetics; as well as data from other studies.
Dr. Butler tested then-new diabetes medication, Januvia, and, in 2008, observed that the drug causes some pancreatic changes that are precursors to pancreatic cancer, according to a The New York Times report. “I knew some stuff that I thought was a worry and I was obliged to pursue it,” Dr. Butler, the chairman of endocrinology at the UCLA, told the Times. Based on Dr. Butler’s study, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) began investigations on the drugs.
In separate reviews, Dr. Butler and colleagues, Public Citizen, and the Institute for Safe Medication Practices (ISMP) each found many more cases of pancreatitis and pancreatic cancer reported for the incretin drugs than for Avandia, another Type 2 diabetes drug, The Times said.
Cohen noted three studies published in 2013 that revealed increased pancreatic risks with incretin therapies. Data included a review of health insurance data revealing a higher risk of hospital admission for acute pancreatitis in patients taking Januvia and Byetta when compared to other diabetes medications, as well as a review of FDA data that revealed increased pancreatitis and pancreatic cancer risks in patients taking incretin mimetics. “The evidence is fiercely contested, with manufacturers stoutly defending the safety of their products,” Cohen wrote, according to MedPage Today.
In an accompanying editorial, BMJ Editor-in-Chief Fiona Godlee, MD, wrote, “instead of engaging in open debate about legitimate and important scientific questions, the manufacturers have been unwilling to share their data. Meanwhile, patients and doctors have not been kept properly informed about the uncertainties surrounding these drugs.” Godlee added, “The debate would be much easier to resolve if all the information was placed in the public domain so scientists, doctors, and, ultimately, patients could make up their own minds,” according to MedPage today.
Pancreatitis is painful, potentially fatal, and a known risk factor for pancreatic cancer. The disorder has also been linked to kidney failure. Other serious side effects associated with these Type 2 diabetes drugs include low blood sugar; anaphylaxis and other allergic reactions, such as hives, rash, swelling of the face, lips, tongue, and/or throat; diseases of the pancreas such as acute, necrotizing, or hemorrhagic pancreatitis; pancreatic cancer; thyroid cancer; vomiting and nausea; anorexia; persistent, severe abdominal pain, sometimes radiating to the back; and death.
More than 100 lawsuits representing 575 plaintiffs nationwide allege injury—typically pancreatitis—due to Byetta, according Bristol-Myers’ latest quarterly regulatory filing; 43 lawsuits claim that Januvia caused pancreatic cancer, according to Merck, wrote The Times.