SGLT2 Inhibitors for Heart Failure

Transcript:

Deepak L. Bhatt, MD, MPH: Let’s get back to SGLT2 [sodium-glucose transporter protein 2] inhibitors, more specifically. Scott, when do you actually suggest adding an SGLT2 inhibitor to the treatment regimen? And in answering that, why do SGLT2 inhibitors even have a role in heart failure? They started out as diabetes drugs, and perhaps many of our primary care practitioners in the audience are still thinking of them as diabetes drugs. But now I guess the heart failure community have co-opted them, and they are also heart failure drugs. When exactly do we use them and why?

Scott David Solomon, MD: I think it’s still a little premature to start thinking about using them broadly in heart failure. They haven’t been approved for that use by the FDA, and they haven’t been reviewed by the guidelines. But as Javed just said, that’s bound to happen very, very soon based on the results of the DAPA-HF trial.

Let me just take a step back and talk a little about SGLT2 inhibitors and why we even studied them in heart failure. It turns out that SGLT2 inhibitors are another type of drug that can lower glucose. They do this by blocking the sodium-glucose transport protein in the kidney that is basically responsible for keeping glucose in the kidney. If you block it, you will actually cause these individuals to lose glucose in the urine. In fact, there is a genetic disorder called renal glycosuria. It’s not really a disorder because it’s benign, and those patients have the same type of phenomenon—they spill glucose when their blood glucose goes over a certain amount.

SGLT2 inhibitors were being tested in the diabetes world for lowering glucose, and the first large trial that finished was the EMPA-REG OUTCOME trial. This trial tested empagliflozin in patients with type 2 diabetes. That trial was stopped for overwhelming efficacy for an endpoint that they didn’t necessarily expect. Many of these diabetes drugs were designed to prove safety, not necessarily efficacy. But in EMPA-REG OUTCOME, they saw a reduction in cardiovascular death and heart failure hospitalization. The heart failure hospitalization reduction was really quite dramatic. Although these weren’t patients with heart failure, they were patients who were at risk for heart failure, and they all had diabetes.

This started a revolution in thinking about how these drugs might [benefit] patients with heart failure. The mechanism was not completely clear. We knew that it wasn’t all about lowering glucose because the benefits seemed independent of the glucose decreasing. But at that point, a number of other trials were initiated to test the drug class in patients who actually had heart failure and did not have type 2 diabetes—in particular, heart failure with reduced ejection fraction. There were also trials of heart failure with preserved ejection fraction. So, a diabetes drug was then tested in patients who didn’t even have type 2 diabetes with the idea that the benefit would extend to them as well.

The first of those trials to show benefit, or to finish, actually, was DAPA-HF, which we presented at the ESC [European Society of Cardiology] Congress. DAPA-HF compared dapagliflozin to placebo in patients with heart failure with reduced ejection fraction and showed a substantial 27% reduction of primary endpoint, which consisted of a composite of cardiovascular death, heart failure hospitalization, and urgent heart failure visits. This was in patients who had type 2 diabetes and in patients who did not have type 2 diabetes. The benefit was identical in those 2 subgroups.

This has changed the way many of us think about how we’re going to treat patients with heart failure in the future. Technically, for patients with diabetes and heart failure, there’s already an indication for an SGLT2 inhibitor. Many of our colleagues are already switching patients who have diabetes and heart failure to an SGLT2 inhibitor. I think there are probably some who are already doing that for patients without diabetes, but there isn’t an indication just yet and the guidelines haven’t yet weighed in. But I think that’s going to happen very soon.

Transcript Edited for Clarity