I really suspect the placebo had to have been active in some way based on the amount of side effects reported from it. It's a very odd thing to see but not uncommon to see placebo slanted in a way that it obscures some of the side effects that are 100% caused by the active ingredients.
The other question I have is that in the 2 year graph, the HBA1C control seems to decrease with longer use. I wonder how that graph would look if it was extended out to 5 years. Would the benefit turn out to be medium term and decrease in the long term as the effects of the medication accumulated? Is it possible there could be a negative effect in a 5 year time window that might mean doctors shouldn't be prescribing to those patients who are in their 30's and 40's? (I know people in their 40's who are on it.)
One other question - have you been following the discussion on risk of going under anesthetic while on it? There is some discussion among anesthesiologists about increased risk of anesthetic complications due to delayed gastric emptying and they don't know the right length of time it should be stopped prior to anesthesia as of yet.
Am also curious your thoughts about those who are using it as a designer drug for weight loss without having tried anything else. Seems to be a bit like a fad in that regard but not without risk?
Ya I suspect that they used the "medication sans active agent" or "excipients" for the placebo. Can't say for sure, but to be more specific the increase in allergic reactions, and AEs leading to discontinuation, which I assume are largely driven by those allergic reactions, is what makes me suspect they may not have been using saline.
I agree the upward slope on the A1C isn't ideal, but I doubt it would ever become a negative effect relative to placebo, with respect to A1C, that is. I'm not sure what to make of that trend, though it does seem to be somewhat consistent across trials. I do have a lot of doubts about putting someone that young on these medications, which is why they fall in the same emergency category as bariatric surgery in my mind.
I'm well aware of the anesthetic risk, I've actually been talking about that regularly with some of my attendings. I plan to go into anesthesiology, and this comes up often as a point of concern with limited data. At some point I may try to do a short post on that issue, but my understanding is that we know very little about how long patients must be off those medications and NPO (eat/drink nothing) prior to procedures in the setting of GLP1 medications.
Definitely not a fan of the designer drug approach. I think the GI side effects + risk of complications are very real, I have a concern regarding protein consumption and maintenance of lean body mass, plenty of other issues. I did hear somewhere that it has anecdotally helped some people break long-standing substance use patterns, which is very interesting, and could be secondary to some CNS effect, but who knows.
They calculated the hazard ratio, which is a relative measure, similar to relative risk. Relative measures can be useful, but I always look at absolute measures as well. Their 2.3% absolute risk reduction for the primary composite looks promising at first glance, but less so once you parse the data, in my opinion.
My point is not that it didn't help, but more so that the claim regarding CV event reduction isn't very strong.
I really suspect the placebo had to have been active in some way based on the amount of side effects reported from it. It's a very odd thing to see but not uncommon to see placebo slanted in a way that it obscures some of the side effects that are 100% caused by the active ingredients.
The other question I have is that in the 2 year graph, the HBA1C control seems to decrease with longer use. I wonder how that graph would look if it was extended out to 5 years. Would the benefit turn out to be medium term and decrease in the long term as the effects of the medication accumulated? Is it possible there could be a negative effect in a 5 year time window that might mean doctors shouldn't be prescribing to those patients who are in their 30's and 40's? (I know people in their 40's who are on it.)
One other question - have you been following the discussion on risk of going under anesthetic while on it? There is some discussion among anesthesiologists about increased risk of anesthetic complications due to delayed gastric emptying and they don't know the right length of time it should be stopped prior to anesthesia as of yet.
Am also curious your thoughts about those who are using it as a designer drug for weight loss without having tried anything else. Seems to be a bit like a fad in that regard but not without risk?
Ya I suspect that they used the "medication sans active agent" or "excipients" for the placebo. Can't say for sure, but to be more specific the increase in allergic reactions, and AEs leading to discontinuation, which I assume are largely driven by those allergic reactions, is what makes me suspect they may not have been using saline.
I agree the upward slope on the A1C isn't ideal, but I doubt it would ever become a negative effect relative to placebo, with respect to A1C, that is. I'm not sure what to make of that trend, though it does seem to be somewhat consistent across trials. I do have a lot of doubts about putting someone that young on these medications, which is why they fall in the same emergency category as bariatric surgery in my mind.
I'm well aware of the anesthetic risk, I've actually been talking about that regularly with some of my attendings. I plan to go into anesthesiology, and this comes up often as a point of concern with limited data. At some point I may try to do a short post on that issue, but my understanding is that we know very little about how long patients must be off those medications and NPO (eat/drink nothing) prior to procedures in the setting of GLP1 medications.
Definitely not a fan of the designer drug approach. I think the GI side effects + risk of complications are very real, I have a concern regarding protein consumption and maintenance of lean body mass, plenty of other issues. I did hear somewhere that it has anecdotally helped some people break long-standing substance use patterns, which is very interesting, and could be secondary to some CNS effect, but who knows.
How did they calculate the 26%?
They calculated the hazard ratio, which is a relative measure, similar to relative risk. Relative measures can be useful, but I always look at absolute measures as well. Their 2.3% absolute risk reduction for the primary composite looks promising at first glance, but less so once you parse the data, in my opinion.
My point is not that it didn't help, but more so that the claim regarding CV event reduction isn't very strong.