Dapagliflozin Q&A with Naeem Khan and Kiersten Combs

Naeem Khan, MD

As the first SGLT2 inhibitor to be examined in a phase 3 trial for a cardiovascular condition, dapagliflozin is a topic of interest for cardiologists, endocrinologists, and primary care physicians alike. 



DAPA-HF results, which were presented at the European Society of Cardiology (ESC) Congress 2019, showed dapagliflozin could reduce death and hospitalizations by 26% in patients with HF and reduced ejection fraction with and without type 2 diabetes. 



With the presentation of DAPA-HF results and a recent fast track designation for treatment of CKD, many have been left wondering what researchers could learn next about the impact of SGLT2 inhibitors and dapagliflozin.

Between sessions at ESC Congress 2019, MD Magazine sat down with Kiersten Combs, US vice president of cardiovascular metabolism, and Naeem Khan, MD, vice president of cardiovascular and metabolism diseases, both of Astrazeneca, to discuss dapagliflozin and its various potentials moving forward.

MD Mag: After the announcing a priority review designation for CKD and the release of DAPA-HF results at ESC Congress 2019, what is next for dapagliflozin?

Combs: We are extremely proud and excited the by data that was presented here for dapagliflozin, not only with the DAPA-HF trial but also we continue to present and produce analyses coming out of our DECLARE-TIMI studies and I think both of those demonstrate really clinically meaningful benefit for physicians with patients with type 2 diabetes but then also now — which is extremely exciting — in patients with heart failure who do not have diabetes.

I absolutely think this is going to be a set change for how dapaglifozin is used and Farxiga is used not only in a primary care setting to lower A1c and having primary physicians think about how they’re lowering A1c and how that mattered. I very much think we will see both endocrinologists and cardiologists take a look at dapagliflozin and how it fits into their patient population because we know patients with diabetes and endocrinologists suffer from the burdens of cardiovascular disease and we know that heart failure is one of the first complications we see in this patient population.

But I will turn it over to Naeem Khan and he can comment on the data.

Khan: What we see when looking at DAPA-HF is a number of results that are very statistically significant with a P-value of 0.00001. So a risk reduction for the primary endpoint of worsening heart failure and CV death. What I would also add onto it is that as you enter the secondary endpoints you also saw benefits and they were looking across pre-specified subgroups. In particular, the subgroups of people we get asked about most are what happened to the people with diabetes and the people who did not have diabetes.

That was definitely a point of interest because is it truly a diabetes drug or is it for heart failure and this addresses the question. In terms of overall risk reduction in people with diabetes you had 25% and in people without you had 27%. So it is truly a heart failure treatment for physicians to help patients.

MD Mag: Other SGLT2 inhibitors are being investigated for cardiovascular benefit, could the benefit we see from dapagliflozin turn out to be a class effect?

Khan: I’d say we’re the first SGLT2 to actively study in people with and without diabetes and we actually have the data for that. I think we’ve seen some interest in diabetes patients on what happens to cardiovascular outcomes, but that seems to be more in line with seeing if SGLT2 provides better cardiovascular outcomes for people with diabetes. But this is about heart failure patients with and without diabetes and for us, we’re at the forefront. We have the information, we know it’s significant and let’s see what the other ones bring.