I don't mean to sound facetious as I'm sure there are risks (thyroid cancer and pancreatitis among others?). It seems like GLP-1s are often beneficial even in unexpected ways (ex this study). Is it because of the drug or because of the populations it's being used on?
Hi Bree--Interestingly in the SELECT trial, rates of pancreatitis were the same in placebo as Wegovy. If there's any thyroid cancer, its effect size can't be measured (too soon), but it would have to be very bad to overcome the lives we are saving now (in the population being studied).
No mention of the side effects of semaglutide? Why? A number get nausea, vomiting, colon and stomach issues where they aren't able to continue with the med or related type meds for weight loss. I get a little frustrated yes if this helps with bad Covid cases. BUT why are the side effects not addressed? At least in this study. Thanks.
I think the thing here is that when the benefit is a reduction in mortality (and for people in this study who got Covid, Covid was the #1 cause of death!), the side effects have to be considered but should not dissuade us from trying these meds for people are at a high risk of death if they don't. There's been a lot on the side effects of these drugs already and so the focus now is on what we get in exchange for that. It's a slam dunk for the SELECT Trial population, albeit 10% of Wegovy recipients had to stop taking it due to those GI side effects (interestingly, 2% in the placebo arm had to stop for GI side effects too...so 8% is there difference there).
Thank you very much for this. What does research say about using compounded forms of this medicine? I know many people who are going that route. Keep us posted!
The compounding thing is something I don't quite get. I think it's probably okay when done properly...but it's likely one of those things where you never 100% can be certain in all places.
You are likely aware that having a break from bisphosphenates can be acceptable, granted the latter remain sequester for a very long time within the bone matrix
I could not find in the body of the text that COVID-19 deaths were decreased from 3.1 to 2%. It did state that those on semaglutide had a reduction of “serious COVID-19–related adverse events” of 3.1 to 2.6%. This presumably means death or hospitalization. This would be an absolute risk reduction (ARR) of 0.5% and a number need to treat of 200. More importantly, this study was performed before the widespread use of vaccines so the benefit will be likely much, much smaller, if at all. The SELECT trial is more hypothesis generating as opposed to conclusive in regard to infectious disease mortality and the benefit of GLP-1 drugs. Clearly, more specifically designed studies should be performed. $10K a year translates to 2.2-4 million dollars over 2 years to prevent one COVID death (depending on a ARR of 0.5 or 0.9 %). The biggest question is how our health care (non)system is going to pay for these miracle drugs.
Those figures come from the following data; 43 Covid-19 deaths among 2108 reported Covid cases in the Semaglutide arm (2% event fatality rate); and 65 Covid-19 deaths among 2150 Covid cases in the placebo arm (3%). I think I had 3.1% in the manuscript because there may have been a typo at some point (66 deaths instead of 65), but in any case it's 3% vs 2%. On just that metric, you get an NNT of 400, but that's really in the first 2 years of the study, or around $20k worth of drug. Thats $8m per life. That's on the high side of a lot of willingness to pay thresholds (wtp), but it's not out of the question for many systems. Now, over a longer period, the NNT on this outcome likely doesn't change as much but costs mount. So then it becomes "unreasonable" on this metric.
But I would just say that this is ONE metric. The benefits on fewer MI and strokes (and how many hospitalizations and deaths are prevented) there are huge benefits to consider. And I think over time, we'll start adding in others--like less dialysis, and even fewer knee replacements. It's going to be a long process to sort out the wtp, and it'll be dynamic as costs change and benefits are better understood.
That's also why I favor rigorous study of drug holidays and dosing changes over time. It might be that people need to be on it for 3-5 years, and then can go to holidays, saving money, without losing the benefit.
In the long run, I think these drugs will see the system money. But in the short term, they'll be costly and we need to figure out how much we can afford.
At least early in the pandemic obesity was strongly associated with increased mortality. Anecdotally, as a hospice provider, all of my younger patients had BMI over 35.
Is there any relation to this success in GLP-1 to the benefits seen in some studies with Metformin for preventing Long COVID? Is there something about these diabetes/weight loss meds that prevent damage? Or is it just lowering the overall risk for the folks who are taking these medications (secondary benefit)?
I'm not sure but one difference is that with the metformin study (which very much impressed me), it was in people who were not already taking it when they caught Covid. So, they initiated it ASAP and took it for 14 days...and even that was fast enough to get an effect. With these meds, it is a weekly injection and I doubt the first dose or two (especially in the lower initial dose) would make a difference. What I found interesting was that in the new study, the Wegovy recipients had only been on it for 1-2 years when they got Covid...and that's not long to have such a dramatic and improved response in Covid outcomes, when you think about.
Exciting finding! Did they parse out body weight in survivors vs non-survivors of Covid? That is, are we seeing a pharmacological effect, or had the survivors lost more weight than non-survivors before infection?
Wow! Fantastic!
We like good news when we can get it
Impressive. Thank you
Crazy, right?
I wonder how much of the benefit, in this case, and other potential cases, is independent of weight loss.
I don't mean to sound facetious as I'm sure there are risks (thyroid cancer and pancreatitis among others?). It seems like GLP-1s are often beneficial even in unexpected ways (ex this study). Is it because of the drug or because of the populations it's being used on?
Hi Bree--Interestingly in the SELECT trial, rates of pancreatitis were the same in placebo as Wegovy. If there's any thyroid cancer, its effect size can't be measured (too soon), but it would have to be very bad to overcome the lives we are saving now (in the population being studied).
Is anyone researching if semaglutide is a viable treatment for long covid ?
I am not sure but they should. It's not easy to do now, but it could be done!
Exciting news and hoping that continued studies will assist in lowering the cost sooner rather than later.
Amen to that.
No mention of the side effects of semaglutide? Why? A number get nausea, vomiting, colon and stomach issues where they aren't able to continue with the med or related type meds for weight loss. I get a little frustrated yes if this helps with bad Covid cases. BUT why are the side effects not addressed? At least in this study. Thanks.
I think the thing here is that when the benefit is a reduction in mortality (and for people in this study who got Covid, Covid was the #1 cause of death!), the side effects have to be considered but should not dissuade us from trying these meds for people are at a high risk of death if they don't. There's been a lot on the side effects of these drugs already and so the focus now is on what we get in exchange for that. It's a slam dunk for the SELECT Trial population, albeit 10% of Wegovy recipients had to stop taking it due to those GI side effects (interestingly, 2% in the placebo arm had to stop for GI side effects too...so 8% is there difference there).
Thank you very much for this. What does research say about using compounded forms of this medicine? I know many people who are going that route. Keep us posted!
The compounding thing is something I don't quite get. I think it's probably okay when done properly...but it's likely one of those things where you never 100% can be certain in all places.
No clear mention if covid benefit was related to weight loss? If so, was there a number?
Really important question????
👍I like your idea of 'Ozempic Holidays'
You are likely aware that having a break from bisphosphenates can be acceptable, granted the latter remain sequester for a very long time within the bone matrix
I could not find in the body of the text that COVID-19 deaths were decreased from 3.1 to 2%. It did state that those on semaglutide had a reduction of “serious COVID-19–related adverse events” of 3.1 to 2.6%. This presumably means death or hospitalization. This would be an absolute risk reduction (ARR) of 0.5% and a number need to treat of 200. More importantly, this study was performed before the widespread use of vaccines so the benefit will be likely much, much smaller, if at all. The SELECT trial is more hypothesis generating as opposed to conclusive in regard to infectious disease mortality and the benefit of GLP-1 drugs. Clearly, more specifically designed studies should be performed. $10K a year translates to 2.2-4 million dollars over 2 years to prevent one COVID death (depending on a ARR of 0.5 or 0.9 %). The biggest question is how our health care (non)system is going to pay for these miracle drugs.
Hi Douglas,
Those figures come from the following data; 43 Covid-19 deaths among 2108 reported Covid cases in the Semaglutide arm (2% event fatality rate); and 65 Covid-19 deaths among 2150 Covid cases in the placebo arm (3%). I think I had 3.1% in the manuscript because there may have been a typo at some point (66 deaths instead of 65), but in any case it's 3% vs 2%. On just that metric, you get an NNT of 400, but that's really in the first 2 years of the study, or around $20k worth of drug. Thats $8m per life. That's on the high side of a lot of willingness to pay thresholds (wtp), but it's not out of the question for many systems. Now, over a longer period, the NNT on this outcome likely doesn't change as much but costs mount. So then it becomes "unreasonable" on this metric.
But I would just say that this is ONE metric. The benefits on fewer MI and strokes (and how many hospitalizations and deaths are prevented) there are huge benefits to consider. And I think over time, we'll start adding in others--like less dialysis, and even fewer knee replacements. It's going to be a long process to sort out the wtp, and it'll be dynamic as costs change and benefits are better understood.
That's also why I favor rigorous study of drug holidays and dosing changes over time. It might be that people need to be on it for 3-5 years, and then can go to holidays, saving money, without losing the benefit.
In the long run, I think these drugs will see the system money. But in the short term, they'll be costly and we need to figure out how much we can afford.
Thanks for this input!
At least early in the pandemic obesity was strongly associated with increased mortality. Anecdotally, as a hospice provider, all of my younger patients had BMI over 35.
yeah that's what I saw. Younger patients who were sick as hell were often obese. Older patients ran the gamut.
Is there any relation to this success in GLP-1 to the benefits seen in some studies with Metformin for preventing Long COVID? Is there something about these diabetes/weight loss meds that prevent damage? Or is it just lowering the overall risk for the folks who are taking these medications (secondary benefit)?
Dr. Crystal,
I'm not sure but one difference is that with the metformin study (which very much impressed me), it was in people who were not already taking it when they caught Covid. So, they initiated it ASAP and took it for 14 days...and even that was fast enough to get an effect. With these meds, it is a weekly injection and I doubt the first dose or two (especially in the lower initial dose) would make a difference. What I found interesting was that in the new study, the Wegovy recipients had only been on it for 1-2 years when they got Covid...and that's not long to have such a dramatic and improved response in Covid outcomes, when you think about.
Exciting finding! Did they parse out body weight in survivors vs non-survivors of Covid? That is, are we seeing a pharmacological effect, or had the survivors lost more weight than non-survivors before infection?
In the Covid part of the study, we do not know. But that's something we can perhaps look into. (The authors may do further work, and I can ask the,).