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FDA has launched an investigation on an unpublished study suggesting that incretin mimetics are associated with pancreatic cancer |
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The US Food and Drug Administration (FDA) is evaluating an increased risk for pancreatitis and precancerous cellular changes called pancreatic-duct metaplasia associated with incretin mimetic drugs used to treat patients with type 2 diabetes. This covers the glucagon-like peptide-1 (GLP-1) agonists and the DPP-4 inhibitors, both relatively new classes of agent used to treat adults with type 2 diabetes. A group of researchers came up with a study showing that there is a link between incretin mimetics and pancreatic cancer.
In the unpublished study, researchers examined a small number of pancreatic tissue specimens taken from patients after they died from unspecific cause. FDA requested the researchers to provide the methodology of the study as well as the tissue samples for further investigation. Incretin mimetic drugs work by mimicking the incretin hormones that are naturally produced to stimulate secretion of insulin in response to a meal. It was known that these agents might increase risk of acute pancreatitis. This is the first time FDA has issued a communication with regard to the potential risk for precancerous findings of the pancreas with incretin mimetics. It emphasizes, however, that it ”has not concluded these drugs may cause or contribute to the development of pancreatic cancer.” According to study leader Dr. Sonal Singh, M.D., M.P.H., an assistant professor in the Division of General Internal Medicine at the John Hopkins University School of Medicine, ”These agents are used by millions of Americans with diabetes. These new diabetes drugs are very effective in lowering blood glucose. However, important safety findings may not have been fully explored and some side effects such as acute pancreatitis didn’t appear until widespread use after approval.” FDA recommends patients to keep taking the prescribing drugs until further notice. FDA notes that it ”has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and healthcare professionals that the agency intends to obtain and evaluate this new information.” FDA says it is continuing to evaluate all available data to further understand this potential safety issue and will participate in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute (NCI) Workshop on Pancreatitis-Diabetes-Pancreatic Cancer in June 2013 to gather and share additional information. FDA will communicate its final conclusions and recommendations when its review is complete or when the agency has additional information to report. From www.diabetesincontrol.com
More Information available on the FDA
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[3-14-2013] The U.S. Food and Drug Administration (FDA) is evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis, or inflammation of the pancreas, and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the Agency can further investigate potential pancreatic toxicity associated with the incretin mimetics. Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. FDA has not reached any new conclusions about safety risks with incretin mimetic drugs. This early communication is intended only to inform the public and health care professionals that the Agency intends to obtain and evaluate this new information. FDA will communicate its final conclusions and recommendations when its review is complete or when the Agency has additional information to report. FDA previously warned the public about postmarketing reports of acute pancreatitis, including fatal and serious nonfatal cases, associated with the use of the incretin mimetic drugs exenatide and sitagliptin. A recently published study that examined insurance records also found the use of exenatide or sitagliptin could double the risk of developing acute pancreatitis.1 The Warnings and Precautions section of the drug labels and the patient Medication Guides for incretin mimetics contain warnings about the risk of acute pancreatitis. FDA has not previously communicated about the potential risk of pre-cancerous findings of the pancreas with incretin mimetics. Further, FDA has not concluded these drugs may cause or contribute to the development of pancreatic cancer. At this time, patients should continue to take their medicine as directed until they talk to their health care professional, and health care professionals should continue to follow the prescribing recommendations in the drug labels. FDA is continuing to evaluate all available data to further understand this potential safety issue. In addition, FDA will participate in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute’s (NCI) Workshop on Pancreatitis-Diabetes-Pancreatic Cancer in June 2013 to gather and share additional information. FDA urges both patients and health care professionals to report adverse events involving incretin mimetics to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of this page. Reference 1. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013 Feb 25:1-6. doi: 10.1001/jamainternmed.2013.2720. [Epub ahead of print]. From http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm ________ På Diabetesforum i Stockholm nämnde föreläsaren professor Edwin Gale om en kommande publikation ett dygn senare i Diabetes ADA. Denna är nu publicerad. Se nedan www och nedan text http://diabetes.diabetesjournals.org/content/early/2013/03/17/db12-1686.abstract Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors
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AbstractControversy exists regarding the potential regenerative influences of incretin therapy on pancreatic β cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age matched organ donors with type 2 diabetes (DM) treated by incretin therapy (n=8) or other therapy (n=12) and non diabetic controls (n=14) reveals a ∼40% increased pancreatic mass in DM treated with incretin therapy with both increased exocrine cell proliferation (p<0.0001) and dysplasia (increased pancreatic intraepithelia neoplasia, p<0.01). Pancreas in DM treated with incretin therapy was notable for α cell hyperplasia and glucagon expressing microadenomas (3/8) and a neuroendocrine tumor. β cell mass was reduced by approximately 60% in those with DM, yet a 6 fold increase was observed in incretin treated subjects although diabetes persists. Endocrine cells co-staining for insulin and glucagon were increased in DM compared to non diabetic controls (p<0.05) and markedly further increased by incretin therapy (p<0.05). In conclusion, in humans, incretin therapy resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia, the latter by α cell hyperplasia with the potential for evolution into neuroendocrine tumors.
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