With NNT of 100 for 0.9 lives saved from all cause mortality, reported in this study, I look pretty hard at side effects of treatment with semaglutide. They can be pretty severe. My 27 year old physical trainer was using that stuff, became chronically constipated and ended up with his appendix removed. I go to askapatient.com and search for the side effects of these meds and it's sobering.
I want to say, that I have enjoyed your reviews. Especially your deep dive and summaries of trials surrounding Entresto, they have been helpful to review. I have been following your work along with the Sensible Medicine folks with a lot of interest. Especially the fact that you are doing any of this while a medical student, I barely could eat three meals a day and finish my regular studying.
For your review, I was a little surprised by your lack of enthusiasm. I feel like following more staunch EBM folks, I worry that can lead us down a nihilist path. I think this trial is fairly impressive, but I think you main frustration was just that the effect size was not as large as you would have hoped. It was interesting to compare your review to Dr. Mandrola’s. https://www.sensible-med.com/p/a-major-breakthrough-in-obesity-treatment?r=oe9qx&utm_campaign=post&utm_medium=web
We have been using GLP-1 for control of T2DM, improvement in surrogate A1C, and now you tell me that it could actually improve mortality? That is just a bonus! I think this is going to have a huge impact if insurance companies are going to cover for people who are prediabetic. Some insurers are only allowing Wegovy, which this is. This 2.4 mg dosing is Wegovy.
Outside of the comment below, people also really want to be on Ozempic/Wegovy. I have patients ask me for it all the time. We understand the GI side effects, and they are obviously more pronounced on the treatment arm. This dose is also the big kid dose of Ozempic.
I share your concern about where patient’s weight is being lost, and would be interested to know about fat vs muscle loss. There is a concern about rebound weight gain if we are to remove these agents.
I was curious if you had any great explanation for that larger fluctuation late in the trial period or any other criticisms that would call anything into question. I share your concern that blinding was difficult to maintain given I suspect many patients might be able to tell given the GI side effects. But, when considering the hard outcomes that seems less of a concern as you note.
Overall, I thought this might have been one you had more enthusiasm for. It is a fairly well run trial, provided some hard outcomes, and for a relatively safe drug that people really want. It really won’t change my practice too much, but I suspect there are fewer and fewer reasons to hold back on GLP-1s for patients with CAD, T2DM, and/or Prediabetes. Thanks for your post.
Thank you for the feedback and thoughtful comment! I actually probably agree with you more than the tone of my post may have let on. It would have been helpful for me to spend a couple paragraphs at the top summarizing how impressive semaglutide is in T2DM especially, but also for weight loss of course.
I view GLP1s as a serious intervention, and generally find myself in the camp of medications being a last resort, but given the reality of health in the US, I think semaglutide is an incredible medication that has the ability to help millions of Americans. I think my opinion may have sounded more bleak than I intended, but that basically reflected that the trial didn't really change my priors, and the magnitude of the cardiovascular protection didn't strike me as a game changer.
It is encouraging to see the improvement in mortality, even if the magnitude wasn't huge. I am very much in favor of using these medications when necessary, with the standard concerns re: cost, overuse, long-term use in younger populations. Thanks again for the comment, always great to hear thoughts.
That is all fair. I strongly agree with your mention of younger populations. Good work in general. I really have enjoyed your reviews relating to Entresto.
With NNT of 100 for 0.9 lives saved from all cause mortality, reported in this study, I look pretty hard at side effects of treatment with semaglutide. They can be pretty severe. My 27 year old physical trainer was using that stuff, became chronically constipated and ended up with his appendix removed. I go to askapatient.com and search for the side effects of these meds and it's sobering.
I want to say, that I have enjoyed your reviews. Especially your deep dive and summaries of trials surrounding Entresto, they have been helpful to review. I have been following your work along with the Sensible Medicine folks with a lot of interest. Especially the fact that you are doing any of this while a medical student, I barely could eat three meals a day and finish my regular studying.
For your review, I was a little surprised by your lack of enthusiasm. I feel like following more staunch EBM folks, I worry that can lead us down a nihilist path. I think this trial is fairly impressive, but I think you main frustration was just that the effect size was not as large as you would have hoped. It was interesting to compare your review to Dr. Mandrola’s. https://www.sensible-med.com/p/a-major-breakthrough-in-obesity-treatment?r=oe9qx&utm_campaign=post&utm_medium=web
We have been using GLP-1 for control of T2DM, improvement in surrogate A1C, and now you tell me that it could actually improve mortality? That is just a bonus! I think this is going to have a huge impact if insurance companies are going to cover for people who are prediabetic. Some insurers are only allowing Wegovy, which this is. This 2.4 mg dosing is Wegovy.
Outside of the comment below, people also really want to be on Ozempic/Wegovy. I have patients ask me for it all the time. We understand the GI side effects, and they are obviously more pronounced on the treatment arm. This dose is also the big kid dose of Ozempic.
I share your concern about where patient’s weight is being lost, and would be interested to know about fat vs muscle loss. There is a concern about rebound weight gain if we are to remove these agents.
I was curious if you had any great explanation for that larger fluctuation late in the trial period or any other criticisms that would call anything into question. I share your concern that blinding was difficult to maintain given I suspect many patients might be able to tell given the GI side effects. But, when considering the hard outcomes that seems less of a concern as you note.
Overall, I thought this might have been one you had more enthusiasm for. It is a fairly well run trial, provided some hard outcomes, and for a relatively safe drug that people really want. It really won’t change my practice too much, but I suspect there are fewer and fewer reasons to hold back on GLP-1s for patients with CAD, T2DM, and/or Prediabetes. Thanks for your post.
Thank you for the feedback and thoughtful comment! I actually probably agree with you more than the tone of my post may have let on. It would have been helpful for me to spend a couple paragraphs at the top summarizing how impressive semaglutide is in T2DM especially, but also for weight loss of course.
I view GLP1s as a serious intervention, and generally find myself in the camp of medications being a last resort, but given the reality of health in the US, I think semaglutide is an incredible medication that has the ability to help millions of Americans. I think my opinion may have sounded more bleak than I intended, but that basically reflected that the trial didn't really change my priors, and the magnitude of the cardiovascular protection didn't strike me as a game changer.
It is encouraging to see the improvement in mortality, even if the magnitude wasn't huge. I am very much in favor of using these medications when necessary, with the standard concerns re: cost, overuse, long-term use in younger populations. Thanks again for the comment, always great to hear thoughts.
That is all fair. I strongly agree with your mention of younger populations. Good work in general. I really have enjoyed your reviews relating to Entresto.