AstraZeneca’s Onglyza (saxagliptin) and Kombiglyza XR (saxagliptin in combination with metformin HCI extended release) are part of a class of medications known as dipeptidyl peptidase-4 (DPP-4) inhibitors, a subclass of Inceretin Mimetics, which are used by individuals suffering from Type 2 diabetes. As diabetic patients don’t produce enough insulin on their own, DPP-4 inhibitors stimulate insulin production in the pancreas after meals are consumed to control blood sugar levels. Unfortunately, these drugs also have extremely harmful side effects which the public has not been adequately warned about, including heart failure, congestive heart failure (CHF), cardiac failure and death.
The problem is, DPP-4s aren’t just involved in the production of insulin. As early as 1994, a study published in the American Journal of Physiology showed that administering the incretin hormone GLP-1 to animals produces quick changes in heart rate and in blood pressure. In 2009, researchers at the University of Pisa (Italy) warned that “the effects of DPP4 inhibition on the immune system have not been extensively investigated.” In 2012, a study conducted by the Canadian Institutes of Health Research noted that “there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease.” They pointed out that incretin hormones were extensively involved in processes in the myocardium and in the vasculature of the heart, arteries, and veins.
In October 2013, AstraZeneca finally published the results of its clinical trial of saxagliptin, called the SAVOR trial (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) in the New England Journal of Medicine. The study was designed to account for “real world” usage of diabetes drugs. In the trial, more than 80% of patients had pre-existing hypertension, 38% had a prior myocardial infarction, and 12.8% pre-existing heart failure. Even with pre-existing conditions accounted for, the study still found that Onglyza use “increased the risk of hospitalization for heart failure.”
FDA Warnings
In March 2013, the FDA issued a Drug Safety Communication, stating that it was reviewing an unpublished study linking the drugs to forms of pancreatic cancer. Another safety communication noting it “requested clinical trial data from the manufacturer of saxagliptin to investigate a possible association between use of the type 2 diabetes drug and heart failure” was published by the FDA in 2014. In April 2015, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee produced a thorough report on Onglyza and Kombiglyze XR which concluded “an increased risk of hospitalization for heart failure was noted in subjects treated with saxagliptin, and FDA sensitivity analyses suggested an increased risk of all-cause mortality in saxagliptin-treated subjects,” and that there was “a public health implication of this finding.”
Finally, in April 2016, the FDA issued a drug safety communication, requiring the Prescribing Information for Onglyza to be revised to include a warning about “heart failure.” Doctors were finally warned to “[c]onsider the risks and benefits of ONGLYZA prior to initiating treatment in patients at a higher risk for heart failure. Observe patients for signs and symptoms of heart failure during therapy.”
Current Status Of Litigation
In February 2018 the claims were centralized into MDL #2809 and transferred all cases to the Eastern District of Kentucky, with all pre-trial activities to be overseen by Chief Judge Karen K. Caldwell. In November of 2018, Judge Caldwell issued a case management order establishing a bifurcated discovery schedule. In January 2022, Judge Caldwell struck plaintiffs epidemiology expert, citing reliance solely on the SAVOR study and not incorporating subsequent human trials. On February 13, 2024 the Sixth Circuit of Appeals denied plaintiffs motion to reconsider, finding that the lower court had properly considered and appropriately applied the law when excluding the expert and granting summary judgement for the defense.
Links:
- https://journals.physiology.org/doi/abs/10.1152/ajpendo.1994.266.3.e459
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528785/
- https://www.nejm.org/doi/full/10.1056/NEJMoa1307684
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-investigating-reports-possible-increased-risk-pancreatitis-and-pre
- http://wayback.archive-it.org/7993/20170112031610/http:/www.fda.gov/Drugs/DrugSafety/ucm385287.htm
- https://www.fdanews.com/ext/resources/files/04-15/04-10-15-Onglyzareview.pdf?1520668813
- https://www.fda.gov/media/96895/download
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022350s014lbl.pdf