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FDA, EMA: Claims that incretin mimetics cause cancer lack data
Assertions that incretin-based drugs could lead to pancreatitis or pancreatic cancer are “inconsistent with the current data,” according to a perspective published by officials from the FDA and the European Medicines Agency in The New England Journal of Medicine.
“These studies suffered, to different degrees, from methodological shortcomings, including limited power, inadequate outcome validation, incomplete covariate ascertainment, and inadequate confounding control,” Amy G. Egan, MD, MPH, of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research, and colleagues wrote.
In April, the FDA announced it would investigate findings that suggested an increased risk for pancreatitis and pancreatic duct metaplasia in patients with type 2 diabetes treated with incretin mimetics, including sitagliptin (Januvia, Merck), liraglutide (Victoza, Novo Nordisk), saxagliptin (Onglyza, AstraZeneca), exenatide (Byetta, AstraZeneca) and exenatide extended-release (Bydureon, AstraZeneca).
The findings were based on a study conducted by researchers at the Johns Hopkins University School of Medicine, published in JAMA Internal Medicine on Feb. 25, 2013.
One year later, both agencies agree that the current data reviewed provides reassurance, but that pancreatitis will continue to be considered a risk associated with incretin-based drugs until further data are available.
“The FDA and EMA believe that the current knowledge is adequately reflected on the product information or labeling, and further harmonization among products is planned in Europe. Ongoing strategies include systematic capture of data on pancreatitis and pancreatic cancer from cardiovascular outcomes trials and ongoing clinical trials, which should facilitate meta-analyses, and accumulation of further knowledge regarding these signals in the future,” they wrote.
For more information:
Egan AG. N Engl J Med. 2014;370:794-797.
FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. Published March 14, 2013.
Singh S. JAMA Intern Med. 2013;doi:10.1001/jamainternmed.2013.2720.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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We are very pleased with the announcement by the FDA and EMA recognizing that current knowledge does not support incretin-based therapy as causing pancreatic cancer. This statement is in line with and in fact validates the findings and conclusions, as it relate to incretin-based therapy, of the recently published American Association of Clinical Endocrinologists (AACE) Consensus on diabetes and cancer. The AACE consensus was based on epidemiology, basic and molecular science, pathophysiology and clinical experience based on available data at the time of publication both from the US and globally. To reach their conclusions, the FDA and EMA were able to further assess large anima-based cellular and pathophysiology data as well as newer large-scale clinical studies, eg, SAVOR and EXAMINE. We also share with the FDA the need to stay cautious and have further long-term studies to provide much needed assurance. This turn of events further underscore the important role of medical societies in reviewing the evidence and coming up with meaningful clinical recommendations on behalf of their members, patients and the public
We all agree that people with obesity and diabetes have a higher risk for cancer. Therefore, the AACE consensus has appropriate recommendations for early cancer screening and suggests management opportunities in the hope to reduce prevalence of cancer in this population. However, the increase in cancer risk in the diabetes population may have been, in part, responsible for the implication of diabetes related drugs and cancer, creating, mostly unsubstantiated inflammatory headlines, scaring patients away from taking the medications. I’m very happy that the FDA, whose cautionary yet alarming announcements in the past may have also added to the public frenzy, are doing the right thing and closing the loop by making their findings public.
The importance of this statement by the FDA is that it brings back confidence in managing diabetes with medication for both clinicians and patients. This comes on the heel of the FDA’s courageous announcement, which I applaud, of the safety of rosiglitazone (Avandia, GlaxoSmithKline) and removal of its REMS. These actions, in my eyes, restore the leadership role of the FDA in the clinical management of patients allowing for proper and safer control of diabetes.