Steve Nissen, MD: SGLT-2 Inhibitors, Then & Now


How the effective cardiovascular drug class have reach a state of impending head-to-head trials.

The sodium glucose co-transporter 2 (SGLT-2) inhibitor drug class has evolved from surprising therapy to the standard-of-care for major adverse cardiovascular event (MACE) prevention and comorbid type 2 diabetes (T2D) treatment in patients with cardiovascular diseases such as atrial fibrillation.

Just years ago, the drug class wasn’t even on clinicians’ radar for the benefits it now serves. In an interview with MD Magazine® while at the American College of Cardiology (ACC) 2019 Scientific Sessions in New Orleans, LA, Steven Nissen, MD, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, discussed the progression of SGLT-2 inhibitors, and how individual therapies have compared thus far.

MD Mag: How do current SGLT-2 inhibitor options compare?

Nissen: Well, the data I think are actually more consistent than inconsistent. Now, it is true there’s different outcomes—in terms of the strength of the evidence— but if you look at the totality of the data, it's very clear that SGLT-2 inhibitors do reduce major adverse cardiovascular events. They appear to significantly reduce hospitalization for heart failure, and they appear to reduce renal deterioration in patients with diabetes.

I don't think we have enough data to say that 1 of these drugs is more superior to the other, has better outcomes than the other, even though there are some differences in the trials. You have to understand that, in these trials, different kinds of patients were enrolled, and so the differences in the patient population may drive the different outcomes.

It really looks like a very good class, and what's interesting about it is nobody saw it coming.

Why is that?

When drugs were being developed—if you go back about 10 years, I was the one that proposed to the Food and Drug Administration that they require cardiovascular outcome trials for diabetes drugs. It was very controversial at the time, but it was because we had some evidence that there were drugs that might lower blood sugar but actually increase adverse cardiovascular events.

And as the drug classes came about, a lot of people thought that the DPP-4 inhibitors would actually prove to be beneficial, and it turns out that they have no benefits whatsoever. They only lower our blood glucose modestly, they have no cardiovascular outcome benefits, and in some cases they actually increaseat least in 1 of the drugs—heart failure.

The SGLT-2 inhibitors—why would anybody expect a drug that makes you leak glucose in the urine, why should that reduce cardiovascular events? But it did, and it's why we proposed doing this in the first place, because until you test these drugs in randomized, controlled trials you really don't know what works and what doesn't work. We got a really interesting result with the SGLT-2 inhibitors, and we got interesting results now with the GLP-1 agonists.

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