Transcript Related Guidelines

For Patients With HFrEF, What Is the Role for and Treatment Pearls for SGLT2 Inhibitors?

Javed Butler, MD, MPH, MBA · University of Mississippi


December 14, 2020

Key Takeaways:

  • The DAPA-HF and EMPEROR-Reduced trials showed statistically significant benefit with SGLT2 inhibitors in patients with HFrEF with regard to clinical outcomes and quality-of-life outcomes.

  • SGLT2 inhibitors are generally well tolerated and are expected to become part of the new foundational standard therapy for heart failure.

This transcript has been edited for clarity.

There's a lot of excitement about the use of SGLT2 inhibitors, with two large multicenter clinical trials of these agents showing positive benefit, not only on clinical outcomes but also on quality-of-life outcomes. Although the new guidelines either in the United States or Europe have not been updated yet, we are waiting to see what the guidelines will say—I will not be surprised that the new foundational standard therapy for heart failure will become a quad therapy with the use of the RAS modulator, evidence-based beta blocker, evidence-based MRA (mineralocorticoid receptor antagonist), and an evidence-based SGLT2 inhibitor. Hopefully, that is the way the science and the clinical practice will evolve; however, now that we have the evidence, the real issue is how quickly can we implement because what we are learning, both in the DAPA-HF and EMPEROR-Reduced trials from the nominal P-value for the Kaplan-Meier curve—in other words—at what time did you achieve a statistically significant result in these trials? In both trials, we saw that it occurred in less than 1 month, so not only is it important to give these therapies, the sooner the better.[1,2] 

A benefit with SGLT2 inhibitors is that it's just one dose—you don't need to uptitrate them. They are pretty well tolerated in terms of reasons people are unable to tolerate other drugs or it makes them more cumbersome (eg, blood pressure, heart rate, serum potassium, and creatinine, and multiple visits for uptitration)—none of those are of particular concern. As I said, it's just one dose. You need to give it in the morning with or without food. The reason you give it in the morning is because you don't want your patient to be waking up in the middle of the night peeing, and because of the osmotic diuresis,[3] it's probably better to give it in the morning. Make sure to give patients instruction about genital hygiene. The trials do not show an increased risk of upper urinary tract infection. However, you do have a risk of genital mycotic infection,[4] so genital hygiene becomes important. Some patients may need antifungal treatment, but this is not a reason not to give these therapies. The risk of hypoglycemia in patients with diabetes is very little and primarily related to those who are also on secretagogues like sulfonylureas or insulin. Again, the risk of ketoacidosis or euglycemic ketoacidosis is very low, but of course, we have to be careful and watch for these. These diabetic complications, obviously, are not issue in patients who do not have diabetes. 

It is up to us to embrace this therapy. If you're uncomfortable, perhaps give it in conjunction with our endocrine or primary care colleagues, but at the end of the day, the cardiologists will have to start owning this therapy—get comfortable with it—and give this therapy to our patients.


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