CV Risk in T2D: Adopting Novel Therapies Into Practice

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Well, that’s a good lead-in. Peter, tell us about the DPP-4s [dipeptidyl peptidase 4 inhibitors] and what happened in heart failure. What’s the story there?

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Recall the DPP-4s, they’re dipeptidyl proteasome inhibitors 4. So they inhibit the breakdown of GLP [glucagon-like peptide].

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: They’re not a GLP-1 agonist.

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Right, but they inhibit. The drugs inhibit the enzyme that breaks down GLP-1. They lower hemoglobin A1C [glycated hemoglobin], are completely neutral on blood pressure and neutral on weight, and were completely neutral on the MACE [major adverse cardiovascular event] outcomes. But again, because of this theme, the reason why people wanted heart failure to be adjudicated is that we had previously seen a signal with the TZD [thiazolidinedione] class, and there was a concern that with drugs that don’t cause hypoglycemia so much, that maybe the MACE is not such an appropriate safety end point. Maybe heart failure should be in there. There was a push to have heart failure in these trials, and with 1 of the DPP-4s, alogliptin, there was a signal that those randomized to alogliptin had a higher rates of heart failure that to this day are not explained. It wasn’t explained in any of the other DPP-4 agents. Now, I imagine with GLP-1s and SGLT2s [sodium-glucose cotransporters 2] coming on, DPP-4 use may trail off right now. But they still have a large percentage use in type 2 diabetes.

Christopher P. Cannon, MD: And saxagliptin and [SAVOR-TIMI 53] was sort of the first problem with heart failure in the DPP-4 class. But then 2 other studies, CARMELINA and TECOS, not seeing it. So it has not been a consistent finding, so it’s a little more confusing. But the lack of cardiovascular benefit has really shifted attention, I think, to these 2 other classes of SGLT2.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Where the benefits are really clear. That debated outcome with heart failure that we saw in the DPP-4s is off the table, positive decrease in heart failure with the SGLT2 inhibitors, no worsening of heart failure, and a trend in the GLP-1 agonist.

So 1 of the things we did was we looked at the ACC [American College of Cardiology] pathway, which was endorsed by the ADA [American Diabetes Association]. And Melissa, I think you know a lot about that. How does that help the clinician?

Melissa L. Magwire, RN, MSN, CDE: We’re actually using that as a foundation for 1 of the programs that we’ve started in our cardiometabolic clinic and really looking at how to drive practice pathways. There is such a plethora of information out there, all these cardiovascular outcome trials, all these medication classes. So these guidelines and this consensus pathway actually is kind of helping home in on if my patient has ASCVD [atherosclerotic cardiovascular disease], what should I consider? If my patient has heart failure, what should I consider? Hopefully, laying out that foundation and a starting point for the clinician to take it and then individualize it for each patient.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: And Peter, that specifically says that if you’re at risk for heart failure or for ESRD [end-stage renal disease], to consider an SGLT2 inhibitor, and if you’re at risk for an atherosclerotic event, consider a GLP-1 agonist. So they’re not really waiting for the heart event; they’re saying even at risk.

Peter McCullough, MD, MPH, FACC, FACP, FAHA, FCCP, FNKF: Right. So these suggested pathways, and we’ve reviewed them, really do encourage the clinician to stylize based on risk. And I agree with your comments as patients map toward atherosclerotic cardiovascular risk, the GLP-1 agonists seem very favorable. For patients who map toward renal and heart failure risks, the SGLT2 inhibitors.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Anything else on these pathways? Do you agree with the other 2 comments?

Christopher P. Cannon, MD: Well, the flow diagrams and the colored pictures are very helpful, and they’ve become reference guides, so that we have things in our white coat—we may have 1 that’s laminated. And so that’s a practical thing that’s helpful because there is so much information. But then you look back, oh yeah, OK. So that’s been a really positive thing in the consensus pathway documents.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: Seth, any comment on ACC pathway?

Seth J. Baum, MD, FACC, FACPM, FAHA, FNLA, FASPC: Yeah, I would just say it’s 1 of the simpler pathways, and it’s easier to follow than some of the other very long algorithmic pathways that we have.

Melissa L. Magwire, RN, MSN, CDE: And it was not simple to get it to that process. I can tell you that. A lot of work went into making it simple.

Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA: But it really does help.

Melissa L. Magwire, RN, MSN, CDE: It was helpful, yes.

Transcript edited for clarity.