Takeda’s Nesina (alogliptin) May Provide Cardiovascular Benefit in Certain Populations

At the end of March, encouraging news about Takeda’s once-daily pill for type 2 diabetes, Nesina (alogliptin), circulated at the American College of Cardiology (ACC) conference in Washington, DC. The buzz surrounded the EXAMINE trial, which studied the long-term cardiovascular safety of Nesina (specifically, the risk of heart attacks, stroke, and death related to a cardiovascular cause) in people who were at high cardiovascular risk and took the drug for up to 3.5 years. Overall, the trial’s main finding, published in the prestigious New England Journal of Medicine, was that Nesina did not increase those cardiovascular adverse outcomes. Later, researchers performed an analysis of the data that looked at various sub-populations in the trial. In that sub-analysis, Nesina seemed to be associated with a lower risk of death related to a cardiovascular cause in certain populations: specifically, women, patients with normal or only mildly impaired kidney function, and people who had type 2 diabetes for less than five years – to us, that sounded like a very large group of patients! Although the results were from a sub-analysis conducted after the trial was completed (a “retrospective” analysis, which is not as reliable as what is called a “prospective” analysis that is designed from the start of the trial), these results are intriguing, especially for the previously mentioned sub-populations. The diabetes community has been waiting to see whether DPP-4 inhibitors like Nesina could actually prevent cardiovascular complications, though the trials reported to date have not shown such a benefit in their overall patient populations and we imagine that a much longer trial would be needed to know if this was the case. Please read our previous update about Nesina and whether it could be considered “cardio-protective” to learn more.

As background, the FDA is requiring virtually all new type 2 diabetes drugs to be tested in cardiovascular outcomes trials, which follow a large population of patients over a long period of time to study cardiovascular safety. This hasn’t been easy for the diabetes community, although we’re very interested to see if any trials prove that the drugs help cardiovascular outcomes longer-term. We certainly hope the trials are long enough. The EXAMINE trial enrolled patients with pre-existing heart disease (meaning they were at high risk for further heart-related complications) for three months (a relatively short period of time compared to a typical cardiovascular outcomes trial), leaving many to question, again, if the drug would have shown a similar cardiovascular benefit if the patients in the study were healthier and/or were followed over a much longer period of time. –NL/AB/KC