FDA warns on heart failure risk associated with Onglyza, Nesina
- The FDA is adding new warnings to the labels for AstraZeneca's Onglyza (saxagliptin) and Takeda's Nesina (alogliptin) after an internal safety review found an increased risk of heart failure with the two diabetes drugs.
- This action follows an April 2015 recommendation by an FDA advisory committee to add a new warning to the drugs’ labels. Data from two large clinical trials informed the regulator’s decision to issue an alert.
- Onglyza and Nesina are part of a class of type 2 diabetes drugs known as dipeptidyl peptidase-4 (DPP-4) inhibitors.
The move comes after the FDA reviewed two studies of the drugs. In a study involving 16,492 patients with Type 2 diabetes, 3.5% of Onglyza-treated patients were hospitalized for heart failure versus 2.8% of placebo-treated patients. The second study involved 5,380 patients, and among this group, 3.9% of Nesina-treated patients were hospitalized compared to 3.3% of placebo-treated patients.
The results of the second study were not statistically significant, which is one reason why FDA experts were more concerned about the safety risks associated with Onglyza. Nonetheless, they decided to put warning labels on both drugs because they are in the same class and the mechanism driving the increased risk is not clear.
The FDA's warning also extends to drugs that contain either saxagliptin or alogliptin. These include Kombiglyze XR (saxagliptin and metformin extended release); Kazano (alogliptin and metformin); and Oseni (alogliptin and pioglitazone).
A physician’s perspective
Dr. Barry Mennen, a Washington, DC-based physician who treats patients with type 2 diabetes, emphasized focusing on absolute risk rather than on relative risk as many physicians are more likely to make decisions based on absolute numbers.
“When I looked at the data from the Onglyza study, I calculated that although the increased relative risk of hospitalization due to HF was 27%, in absolute terms, the risk was 3.4% in the saxagliptin group, and 2.7% in the placebo group. The difference in absolute risk is less than 1%," Mennen said. (FDA warning cited 3.5% and 2.8%, respectively.)
Mennen also pointed out that number needed to treat (NNT) analysis is a key driver in physician decision-making.
“Based on the outcomes, the NNT is 142 patients. So, you need to treat 142 patients with saxagliptin to wind up with one patient hospitalized with HF. But those 142 patients represent all patients in the study," he explained. "If we just look at the patients at increased risk of heart failure, including those with hypertension, history of acute coronary syndrome, valvular heart disease, coronary artery disease, etc., and remove them, the NNT would undoubtedly increase significantly.”
Based on the new information and his own analysis, Mennen said that patients with type 2 diabetes and one or more risk factors for heart failure might be better treated with another drug. However, for those without risk factors, he believed saxagliptin and other drugs in this class remained "excellent" drugs for type 2 diabetes treatment.