Federal regulators just requested that AstraZeneca Pharmaceuticals LP and Bristol-Myers Squibb Company conduct a clinical trial on two of its Type II diabetes drugs, Onglyza and Kombiglyze XR, due to serious cardiac reactions associated with the medications.
Onglyza and Kombiglyze XR are also known under the generic name, saxagliptin, and are incretin mimetics, which are GLP-1-based diabetes therapies made with natural substances that reduce increased blood sugar levels. The drugs, along with all other incretin mimetics, have also been associated with other adverse health reactions, particularly to the pancreas, such as pancreatitis, a known pancreatic cancer precursor.
The U.S. Food and Drug Administration (FDA) request came after release of a study published in the New England Journal of Medicine (NEJM) that found that in patients taking Onglyza and Kombiglyze XR, an increased hospitalization rate for heart failure occurred. Heart failure involves the heart not appropriately pumping blood through the body.
It is expected that the trial data will be provided by early March 2014, at which point, the FDA will be conducting a thorough review and will release its findings. The FDA considers the NEJM data preliminary and indicated that a review of the drug’s clinical trial data is part of a larger review of all Type 2 diabetes drug treatments and cardiovascular risks.
Meanwhile prior studies have revealed associations between Type 2 diabetes medications, known as incretin mimetics, including Onglyza and Kombiglyze XR, which have been tied to increased risks of developing pancreatitis. In fact, the drugs were among various diabetes drugs reviewed in a study that reviewed adverse drug reaction reports (ADRs), according to Italian researchers who validated the connection between the diabetes drugs and pancreatic damage, a prior AdverseEvents report indicated. Study results were published in the November 13, 2013 issue of Informa Healthcare.
Another study published in the journal, BMJ, revealed that incretin mimetics, such as Onglyza and Kombiglyze XR, might be riskier than first believed. That report also revealed that drug makers of incretin mimetics withheld information on the potentially dangerous effects of this class of drugs. After a review of thousands of pages of regulatory documents obtained under Freedom of Information rules, BMJ located unpublished data indicating that “unwanted proliferative or inflammatory pancreatic effects,” are associated with use of incretin mimetics.
Another study that was published March 22, 2013 in the journal, Diabetes, indicated that abnormal changes, including pre-cancerous lesions, in the pancreases of eight people who had taken GLP-1-based medications, when compared with patients who took other diabetes medications, according to a prior report by Medscape Medical News.
FDA Adverse Event Reporting System (FAERS) data from November 1, 1997 to December 31, 2012 that was aggregated and standardized by the AdverseEvent RxFilter process, revealed 4,512 reports of pancreatitis and 14 cases of elevated pancreatic enzyme levels in which incretin mimetics were indicated as the primary suspect. Of these, the team identified 2,478 hospitalizations and 113 deaths in which incretin mimetics were indicated as the primary suspect.
The FDA issued a Drug Safety Communication in March 2013 that stated that the agency was “…investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes.”