Dr Darren K. McGuire Debates SGLT2 Inhibitors and GLP-1 Receptor Agonists as CVD Prime Time Prevention

June 12, 2020

In a debate at the American Diabetes Association 80th Scientific Sessions, Darren K. McGuire, MD, MHSc, professor of medicine in the Division of Cardiology, Dallas Heart Ball Chair for Research on Heart Disease in Women, Distinguished Teaching Professor, at the University of Texas Southwestern Medical Center, will discuss whether sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are ready to be used for primary cardiovascular prevention.

During the 2020 American Diabetes Association 80th Scientific Sessions, Darren K. McGuire, MD, MHSc, professor of medicine in the Division of Cardiology, Dallas Heart Ball Chair for Research on Heart Disease in Women, Distinguished Teaching Professor, at the University of Texas Southwestern Medical Center, will take part in a debate about whether sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are ready for "prime time" in cardiovascular primary prevention.

Transcript

At ADA, you will take part in a debate about SGLT2 inhibitors and GLP-1 receptor agonists and whether or not they're ready for prime time in cardiovascular prevention. What will that discussion look like?

So, the upcoming ADA, I'll be debating Mikhail Kosiborod [MD] about whether the SGLT2 inhibitors and/or the GLP-1 receptor agonists are ready for prime time for primary prevention of adverse chronic cardiovascular disease. I've worked very closely with Mikhail for over 20 years, we're very close friends, and I look forward to humiliating him on the international stage.

So, I've assigned [to take the position] that they're not ready for prime time. In most of my answer, I think that SGLT2 inhibitors from the DECLARE in the CANVAS trials data pretty clearly don't affect atherosclerotic cardiovascular disease risk in the primary prevention population. So, I think that's a reasonably easy answer if we're talking about 3-point MACE [major adverse cardiac event] cardiovascular death, MI [myocardial infarction, and stroke.

The counter to that is in the GLP-1receptor agonist, in general, and the meta-analysis and specifically with dulaglutide and the REWIND trial, the efficacy for cardiovascular atherosclerotic cardiovascular disease outcomes looks to be independent of prevalent atherosclerotic cardiovascular disease (ASCVD). But importantly in REWIND, if you look into the details of the data, the absolute risk reduction in the primary prevention cohort was 0.5%. So, that means you have to treat 200 patients for 3 years to derive that single clinical event reduced, for a drug that's priced often at $300 or $400 a month. It becomes cost prohibitive. So, I'm going to use an economics argument for the GLP-1 receptor agonist.

Now, flipping back to the SGLT2 inhibitors. If we're talking about primary prevention of cardiovascular death, MI, and stroke, it's a reasonably easy answer. It's a very different answer, if you look at heart failure. So, I think that the SGLT inhibitors are, in fact, ready for prime time for heart failure risk reduction independent of prevalent ASCVD. I think probably will need to have multiple risk factors just to get to a level of absolute risk that will justify the absolute risk reduction and the cost efficiency. So, I don't think every single patient with type 2 diabetes should be started on an SGLT2 inhibitor to prevent heart failure, but I think we should have a very low bar and not require clinically manifest cardiovascular disease to trigger that decision.