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The GLP-1 Diabetes Medications – Mechanism of Action

Byetta, Januvia, Victoza, Tradjenta and Onglyza each target GLP-1 (glucagon-like peptide-1) for their intended mechanism of action. Diabetics, for different medical reasons, generally have inadequate amounts of insulin available for the digestion of sugar. Consequently, blood sugar levels of diabetics can be abnormally, and sometimes dangerously, high.
When released by the presence of food, GLP-1 signals the body to release insulin so sugars can be readily digested. Oversimplified, more GLP-1 means more insulin. So diabetics, whose insulin levels are abnormally low, will benefit if their levels of GLP-1 hormone are increased thereby signaling the body to make more insulin available, compensating for the diabetic’s otherwise insufficient amount.

At the physiological level, the GLP-1 agents fall into two categories: those that mimic GLP-1 and those that inhibit the body’s normal suppression of GLP-1. The injectible GLP-1 agents Byetta and Victoza are synthetic agents that are designed to mimic the action of GLP-1. Januvia, on the other hand, is designed to suppress the body’s mechanism that would otherwise stop the release of insulin. Either way, the GLP-1 agents enable the body to release higher amounts of insulin so blood sugar levels can be maintained within a safe range. 

Recent Studies Signaling Association with Pancreatic and Thyroid Cancers

            In July, 2011 a study conducted by investigators at the University of California in Los Angeles concluded that “Use of sitagliptin [Januvia] or exenatide [Byetta] increased the odds ratio for reported pancreatitis 6-fold as compared with other therapies…Pancreatic cancer was more commonly reported among patients who took sitagliptin [Januvia] or exenatide [Byetta] as compared with other therapies. Pancreatitis, Pancreatic and Thyroid Cancer with Glucagon-Like Peptide-1-Based-Therapies, Elashoff et al, 141 Gastroenterology, 150-156 July, 2011.

            In February, 2013, a population-based matched case-control study conducted by researchers at the The Johns Hopkins University School of Medicine concluded that study patients taking sitagliptin [Januvia] or exenatide [Byetta] were twice as likely to be hospitalized for acute pancreatitis than control-patients who were not taking such drugs and, after developing pancreatitis, were 2.84 times more likely to develop biliary and pancreatic cancer than those not taking such drugs. Glcagonlike Peptide 1-Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus Singh et al, published February 25, 2013 online at

            In April, 2013, QuarterWatch, published by the Institute for Safe Medication Practices, released “Perspectives on GLP-1 Agents for Diabetes” in which it reported the results of its “disproportionality analysis of domestic [US], serious adverse events reports for five GLP-1 agents from July 1, 2011 through June 30, 2012.” [at page 2]. Quarterwatch concluded that “the adjusted odds ratio for the GLP-1 group compared to the diabetes drug controls was…25.6” and that “[t]he two injectible GLP-1 analogs [Byetta and Victoza]…were associated with reports of thyroid cancer.” [at page 2].

FDA’s Drug Safety Communication
            On March 14, 2013, the FDA announced that it was “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 [GLP-1 agents].” The Drug Safety Communication indicates that “FDA has not reached any new conclusions about safety risks with incretin mimetic drugs.” FDA Drug Safety Communication March 14, 2013.

No-Cost Review:
If you or a loved one developed pancreatic or thyroid cancer while being treated with Byetta, Januvia and/or Victoza, we would like to speak with you. Please send us your contact information and we will contact you within 24 hours

Patients should continue taking their medications as directed until they talk to their health care professionals

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If you or a loved one developed pancreatic or thyroid cancer while being treated with Byetta, Januvia and/or Victoza, we would like to speak with you. Please send us your contact information and we will contact you within 24 hours

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