The American Diabetes Association (ADA) is calling for all pharmaceutical companies involved in the development or marketing of incretin-based diabetes drugs to make patient-level data on their products available for an independent review that could help settle the question of whether such therapies contribute to the development of pancreatitis or pancreatic cancer.
The move comes as BMJ published an in-depth investigation of this issue yesterday and a UK Channel 4 documentary on the topic aired last night.
Incretin therapy refers to medications such as the glucagonlike peptide-1 (GLP-1) agonists and dipeptidyl peptidase (DPP-4) inhibitors, which are used in type 2 diabetes, either alone or in conjunction with other medications such as metformin or insulin.
"Recent publications have intensified the controversy surrounding the potential role of incretin therapy in the development of pancreatitis and pancreatic neoplasia in people with type 2 diabetes," the ADA observes.
"People who are taking these medications or who may consider taking them should have the benefit of all that is currently known about their risks and advantages in order to make the best possible decisions about their treatment and care in consultation with their health care providers," says Robert Ratner, MD, ADA chief scientific and medical officer, in a statement.
The ADA says it wants all pharmaceutical companies with incretin therapies to make patient-level data available on all subjects involved in regulatory trials for an independent analysis. It plans to call for applications from academic and research organizations capable of integrating large experimental databases "to illuminate the potential role of incretin therapy in pancreatic pathology."
Diets, Drugs, and Obesity: Dispatches Program Airs in United Kingdom
Meanwhile, the UK Dispatches program that aired last night (viewable only in the United Kingdom) included an interview with Peter Butler, MD, from the University of California, Los Angeles, who first saw changes in the pancreases of rats with these medications.
Dr. Butler has now found evidence of an increase in the size of the pancreas, of about 40%, in human organ donors who had diabetes and were taking these agents (7 on sitagliptin [Januvia, Merck], 1 on exenatide [Byetta, Amylin/Lilly]), as well as a 500% increase in the number of alpha cells in these pancreases, research that was published earlier this year.
Deborah Cohen, MD, BMJ investigations editor, who narrates the documentary, acknowledges that the Food and Drug Administration (FDA) and European Medicines Agency (EMA) are "evaluating Prof. Butler's findings," and some balance is provided in the program in the form of an interview with Richard Holt, MD, from the University of Southampton, United Kingdom.
"This is an emerging story; it's often very difficult to tease out what is a drug effect as opposed to what is a disease effect," says Dr. Holt, noting that patients with diabetes are at increased risk for pancreatitis compared with the general population.
"There may be other aspects of these individuals that may account for some of these signals that are not related to the drug itself. These are rare side effects, and when you are seeing a patient, you are having to balance these relatively rare but potentially serious side effects against the benefits," he observes.
Off-Label Use of GLP-1 Agents for Weight Loss
Of some concern, however, is the fact that during the course of the documentary, Dr. Cohen manages to purchase online the GLP-1 agonist liraglutide (Victoza, Novo Nordisk) for weight loss, an off-label use.
She notes that this is a new indication being pursued by Novo Nordisk, which is evaluating a higher dose of the drug for obesity than is currently used for diabetes.
"The GLP-1–based drugs have the power to make diabetes more manageable and in the long run, perhaps, to help obese people to get slim, but all drug licensing is about judging benefits against potential risks," says Dr. Cohen. "The question now is whether the balance is right on GLP-1–based drugs," she concludes.
Dr. Cohen has reported no relevant financial relationships.
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Cite this: ADA: Independent Review of Incretins and Pancreatitis, Cancer - Medscape - Jun 11, 2013.