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Drs Piña and Kosiborod discuss semaglutide in obesity-related HF with and without diabetes. Both STEP HFpEF trials show similar HF benefits despite less weight loss in patients with diabetes.
https://www.medscape.com/viewarticle/semaglutide-benefits-hfpef-take-step-beyond-weight-loss-2024a10006z2?src=soc_yt
-- TRANSCRIPT --
Ileana L. Piña, MD, MPH: Hello, and welcome to my blog. Today, I'm at the American College of Cardiology in Atlanta. I want to introduce and welcome Dr Kosiborod: from the Mid America Heart Institute, who has presented a very impactful paper, STEP HFpEF DM, that is in The New England Journal of Medicine right now. This is about semaglutide. A lot of patients ask me to give them that pill that makes them lose weight. I see primarily patients with heart failure (HF). So, Mikhail, congratulations on your presentation. Give us a little synopsis of what the trial is about.
The STEP HFpEF Program
Mikhail N. Kosiborod, MD: First of all, it is always a pleasure to be with you. Maybe a quick word about the STEP HFpEF program that included two trials: The first is STEP HFpEF, which was a trial of patients with obesity-related HF with preserved ejection fraction (HFpEF) who did not have diabetes, which we presented and published at European Society of Cardiology in August last year.
The second installment of the program is the STEP HFpEF diabetes trial, which is essentially the same population of patients except they also have type 2 diabetes. I guess your question would be why we did two trials instead of just doing one trial that included patients, both with and without diabetes. I'll come back to that shortly.
The crux of the hypothesis behind the program is that we all know the prevalence of HFpEF has increased dramatically in the past couple of decades. When I was a fellow in training, it was rare for me to see a patient with HF who had preserved EF. A majority of patients had HF with reduced EF. Now, the majority of people we see have HFpEF: Why did that happen? There are a lot of different reasons for the dramatic change in epidemiology. But certainly, one of them, at least in our opinion, is that the obesity epidemic has a lot to do with it. In fact, if you look at the population of patients with HFpEF in the United States, 80% of them are living with overweight or obesity. The hypothesis behind the program was that obesity is not just a comorbidity. It doesn't just happen to coexist by accident in this patient population, it may in fact be causing their HF. It may be a critical factor in the development and progression of HFpEF.
In order to test our hypotheses, patients were randomly assigned to semaglutide, with the target dose of 2.4 mg once a week or matching placebo and treated for 52 weeks, or 1 year. The reason we did two separate trials is because part of that hypothesis was that if obesity is in fact the cause of HF, then certainly, weight loss would be probably not the only factor but "an important factor in the potential benefits of semaglutide in this patient population, provided that semaglutide is beneficial which of course we ultimately demonstrated.
But what we knew from weight-loss trials — not HF trials but weight-loss trials of medications like semaglutide and also other anti-obesity medications like tirzepatide and others — is that people with diabetes tend to lose a lot less weight. With these medications, there's about a 40% less weight loss in people with type 2 diabetes. Lots of theoretical reasons why that could be the case. Nobody really knows for sure.
We knew from the beginning that the weight loss likely was going to be different. Then, of course, there are other things that happen in people with diabetes: They have more severe HFpEF phenotype, and people with more severe disease sometimes don't respond to treatment the same way as those with less severe disease. Finally, we knew when we started the trial, which was back around 2019, 2020, that people with diabetes would be more likely to be treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. At the time, we didn't have the data for SLT2 inhibitors in HFpEF, but we knew that were going to be tested. There was, of course, an expectation that they may well be beneficial. For all of these reasons, we said, "You know what, the treatment effects may well be different between the patient population, but let's study them separately."
Transcript in its entirety can be found by clicking here:
https://www.medscape.com/viewarticle/semaglutide-benefits-hfpef-take-step-beyond-weight-loss-2024a10006z2?src=soc_yt
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