EMPA-REG Trial: Implications for Type 2 Diabetes Treatment, CV Risk Reduction

At the American Heart Association's Scientific Sessions 2017, Eliot A. Brinton, MD, FAHA, FNLA, president of the Utah Lipid Center, discussed how the EMPA-REG trial has been a huge step forward for health care providers being able to put patients with type 2 diabetes onto treatments that can also reduce cardiovascular disease risk.

Transcript

The whole issue of cardiovascular disease in patients with diabetes is one that we have known for decades is so important. It has always been the primary cause of death in a patient with type 2 diabetes an also the primary source of morbidity. So, somebody who has type 2 diabetes is at high risk of heart attack, stroke, and other related macrovascular diseases. So, the question is how do we address that? For many years we’ve had the theory that just lowering glucose is adequate because there is a relationship between glucose levels and macrovascular disease or cardiovascular disease—that we’ve known.

We’ve also had several medications over the years that have had some evidence for lowering cardiovascular events. What we’ve had most recently is a very large, very convincing cardiovascular outcomes trial in the contemporary environment, where we’re using a lot statins a lot of [angiotensin-converting-enzyme] inhibitors—we haven’t had this in the earlier trials—but EMPA-REG in particular was groundbreaking in that a new class of agents—the SGLT2 inhibitors, [in this case] empagliflozin, in a large cardiovascular outcomes trial that looks at these end points in this setting in a randomized, double-blinded trial. And what that trial has shown is convincing evidence for reduction of cardiovascular events in general, and in particular cardiovascular death, which is our most import cardiovascular end point. So EMPA-REG is a huge step forward in terms of our ability to take a patient with type 2 diabetes, put them on an agent and reduce this very large problem of cardiovascular disease risk.

What we’re seeing with EMPA-REG is not only the initial results, but we’re getting deeper into the data. We're looking more carefully at what did go down, what didn’t go down; what were the benefits; were there any risks associated … The quick answer is [there were] many more benefits than risks, but we’re looking more carefully there. And what we’re beginning to get at—and this is one of our most important questions—what is the mechanism? How is it that empagliflozin does what it does? We know for a fact that every drug that lowers glucose does not lower cardiovascular disease. We’ve proven that many times over.

So, EMPA-REG as a trial and empagliflozin as an agent break through the barrier of no relationship, which we’ve seen in many trials recently, to show benefit. And the question is whyis that true. What is the mech can we understand that to better focus our treatment in the right patients to better achieve this reduction in cardiovascular risk that we very much want to achieve in our patients with type 2 diabetes. So, EMPA REG was a breakthrough study, and now we’re getting further into the details of learning things of clinical and hopefully of mechanistic importance.