Brand new high-quality data indicate that semaglutide (the generic name for the blockbuster diabetes and obesity medication Ozempic) is effective in improving symptoms of a certain hard-to-treat type of heart failure. The just-released study—a double-blinded placebo-controlled randomized clinical trial of obese adults—appears in the
Promising. But Jeremy: while I greatly look forward to your emails... two versions of the same one whenever you send? People will talk. ;)
And that's the problem: the talk version, which I don't listen to. Nor, I suspect, do many of your readers. Perhaps simply offer an audio option within the text mail? Or offer a choice on your Substack homepage? But please: not two emails for each post...
Thanks for the feedback, Peter. For the most part Substack is very easy to use. This one thing seems to be a pain because I can't easily embed the audio into the main article *and have it available for upgraded readers only without causing another problem. The problem that causes is that I can put audio below a paywall. But even I put it at the very end of the article, it would hide the comments section. I suspect some free readers read the comments. And in fact, I suspect that some free readers upgrade because they see the quality of the comments (and hopefully that I'm responsive). So I don't want to lose that. BUT I think I have a solution to this problem, which will be to stick it in the headers. Paid readers get a different header and I could put a link to the audio there. Working on it!
And you succeeded! Apologies that I didn't respond to you earlier -- apparently SS is not telling me when I have replies to comments. For the most part, probably a good thing, LOL.
This may be a dumb question, but is obesity a symptom of metabolic syndrome or is it a/the cause?
I ask that because I started out with the question of whether the HF related benefits come from weight loss or if the semaglutide specifically treats the HF, and realized there was a broader question. Were the HF-related benefits the same for people who weren't obese, or did the study design not include that group of people?
I'm guessing that one or more of the articles addresses it, but I haven't had time to look and guessed you had already considered this. Thanks for a great article! I've actually been considering talking to my internist about whether to start semaglutide.
Everyone in the study had obesity. I'm interested if theres a higher effect in folks with BMI above 35 or 40, vs 30. Or is it just a matter of the endpoint? Not sure!
I partially answered my own question (at least with respect to the study design):
We randomly assigned 529 patients who had heart failure with preserved ejection fraction and ***a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher*** to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks.
"Mikhail Kosiborod: It’s not an accident that majority of patients with this type of heart failure have obesity. Obesity is in fact causing it. That realization has not really occurred until now."
Looking forward to reading this, thanks for the heads up. This CHF exacerbation reduction sounds like RR >95%? That is huge.
Previous study also released recently showed about 20% RR reduction in CV events right?
I have to admit that it is satisfying to facilitate unprecedented success with weight loss for patients with this, mounjaro, etc. I decline to prescribe phentermine but these Glp-1 agonists are truly game changing. I always review possible side effects and ask them to spend some time self educating on the manufacturer’s website, instructional videos etc
But if I wanted to, I could easily set up a practice based on these drugs full time. But then i’d miss the full scope of medicine.
Here’s to less chf in the ER 🤞 and all the benefits that go with weight loss
The part that blew me away was the figure in the supplement where you can see the CHF exacerbation kaplan meier curve still going up month after month all the way to the study's end. Whereas the GLP1 group had no more events after 8 weeks. Zero. Like woah.
Just looked at the source NEJM article. Impressive reductions in symptoms, and increased functional capacity. But I don’t see the study authors discussing this hospital/ER visit reduction except for a brief mention:
“ In total, 1 participant in the semaglutide group and 12 in the placebo group had an adjudicated event of hospitalization for heart failure or an urgent visit (hazard ratio, 0.08; 95% CI, 0.00 to 0.42) “
If this 1 vs 12 out of about 260 in each group is statistically significant , then back of a napkin calculation gives us a NNT of about 22? Still pretty good
I wonder how it works in super high risk patients. We know there's population of patients who has a few CHF admissions *per year*. What will this do for them? That said, I think the more frequent admissions is in HFrEF, but I don't have data in front of me on that. But that seems right, right?
Doctor, thank you for your Preprint powered analysis of the NEJM reported double-blind' data.
"Semaglutide" ... got it.
I'm generally fairly cautious on hype. But this one is getting me excited for the fact that so many people could have such measurable differences.
Promising. But Jeremy: while I greatly look forward to your emails... two versions of the same one whenever you send? People will talk. ;)
And that's the problem: the talk version, which I don't listen to. Nor, I suspect, do many of your readers. Perhaps simply offer an audio option within the text mail? Or offer a choice on your Substack homepage? But please: not two emails for each post...
Thanks for the feedback, Peter. For the most part Substack is very easy to use. This one thing seems to be a pain because I can't easily embed the audio into the main article *and have it available for upgraded readers only without causing another problem. The problem that causes is that I can put audio below a paywall. But even I put it at the very end of the article, it would hide the comments section. I suspect some free readers read the comments. And in fact, I suspect that some free readers upgrade because they see the quality of the comments (and hopefully that I'm responsive). So I don't want to lose that. BUT I think I have a solution to this problem, which will be to stick it in the headers. Paid readers get a different header and I could put a link to the audio there. Working on it!
And you succeeded! Apologies that I didn't respond to you earlier -- apparently SS is not telling me when I have replies to comments. For the most part, probably a good thing, LOL.
Keep up the terrific work, all best, Peter
This may be a dumb question, but is obesity a symptom of metabolic syndrome or is it a/the cause?
I ask that because I started out with the question of whether the HF related benefits come from weight loss or if the semaglutide specifically treats the HF, and realized there was a broader question. Were the HF-related benefits the same for people who weren't obese, or did the study design not include that group of people?
I'm guessing that one or more of the articles addresses it, but I haven't had time to look and guessed you had already considered this. Thanks for a great article! I've actually been considering talking to my internist about whether to start semaglutide.
Everyone in the study had obesity. I'm interested if theres a higher effect in folks with BMI above 35 or 40, vs 30. Or is it just a matter of the endpoint? Not sure!
I partially answered my own question (at least with respect to the study design):
We randomly assigned 529 patients who had heart failure with preserved ejection fraction and ***a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher*** to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks.
There was a related interview with the lead author of the study that I think suggests an ultimate answer:
https://www.nejm.org/doi/full/10.1056/NEJMp2307349?query=recirc_curatedRelated_article
"Mikhail Kosiborod: It’s not an accident that majority of patients with this type of heart failure have obesity. Obesity is in fact causing it. That realization has not really occurred until now."
Looking forward to reading this, thanks for the heads up. This CHF exacerbation reduction sounds like RR >95%? That is huge.
Previous study also released recently showed about 20% RR reduction in CV events right?
I have to admit that it is satisfying to facilitate unprecedented success with weight loss for patients with this, mounjaro, etc. I decline to prescribe phentermine but these Glp-1 agonists are truly game changing. I always review possible side effects and ask them to spend some time self educating on the manufacturer’s website, instructional videos etc
But if I wanted to, I could easily set up a practice based on these drugs full time. But then i’d miss the full scope of medicine.
Here’s to less chf in the ER 🤞 and all the benefits that go with weight loss
The part that blew me away was the figure in the supplement where you can see the CHF exacerbation kaplan meier curve still going up month after month all the way to the study's end. Whereas the GLP1 group had no more events after 8 weeks. Zero. Like woah.
Just looked at the source NEJM article. Impressive reductions in symptoms, and increased functional capacity. But I don’t see the study authors discussing this hospital/ER visit reduction except for a brief mention:
“ In total, 1 participant in the semaglutide group and 12 in the placebo group had an adjudicated event of hospitalization for heart failure or an urgent visit (hazard ratio, 0.08; 95% CI, 0.00 to 0.42) “
If this 1 vs 12 out of about 260 in each group is statistically significant , then back of a napkin calculation gives us a NNT of about 22? Still pretty good
I wonder how it works in super high risk patients. We know there's population of patients who has a few CHF admissions *per year*. What will this do for them? That said, I think the more frequent admissions is in HFrEF, but I don't have data in front of me on that. But that seems right, right?
Wow! Love this!