Agree that it's still a new drug and there will be unknown unknowns. Personally, I see myself being less enthusiastic with the incretin hormones e.g. loss of lean body mass. I am concerned seeing otherwise young and "healthy" people jump to glp1s, essentially committing to years/decades to long term usage. Side effects are a certainty with risk that increases with duration of exposure. On the flip side, I'm concerned about its use in the geriatric population also whose lean mass and strength is important, and using GLP1s may be counter productive. There is no free lunch.
I'd love to see Sensible Medicine engage more sensibly on the topic of obesity. The "click" you mention..... isn't it something like 5% of all dieters maintain their weight loss long term? That's a pretty small number of people. And most people who lose weight gain it back plus more. So, to the extent obesity is a problem it seems like a more reasonable treatment goal is weight maintenance rather than weight loss. Then you have to look at the pipeline from dieting to eating disorders, and weigh the real harms of eating disorders. Please please please bring Ragen Chastain (she writes Substack "Weight and Healthcare") to one of your panels for a discussion.
The “long term use” of any therapy will run into some of the same limitations you noted here: specifically, what happens after you exceed the follow up duration from the landmark trials? I suspect this concern will apply to nearly any medicine for any chronic condition. Statins, ACE inhibitors, beta blockers…DOACs….heck even ASA for secondary prevention…. Do you really know that the benefit persists even decades after initiation? No….and you can’t know, since it hasn’t been studied.
What does seem clear is that GLP-1 analogues do NOT have any legacy effect. But that’s not a knock against them…most drugs only work when you are actively taking them.
"What I mean is that patients that I have seen who have lost weight and maintained it with lifestyle change have something click." - This might be well worth understanding. The drugs have really altered some balance, perhaps forever.
This topic of GLP-1 Receptor Agonist also deserves its own Sensible Medicine podcast for the rampant obesity and diabetes epidemic we see in first world countries.
Why not take a further step back and ask yourself, the fact that people would rather take a pill than do basic activities, how fucking profoundly sick are we?
Coffin's already sealed, my friend. Doctors like you need to call it, and you probably won't because you're so entrenched.
1. Why do you assume it's not a durable effect? The trials of discontinuation that I'm familiar with were blinded, i.e. the patients didn't ever attempt to transition to "maintenance". I've had luck with many patients when they know they are going off the drug.
2. I take anti-hypertensives and they normalize my blood pressure. Should I be disappointed that there was no "click"? (I plan to take indefinitely).
3. Why is obesity somehow due to poor will power, but hypertension isn't? I suppose we're going back to treating alcohol use disorder as a defect of character, like obesity. Why can't we add diabetes and hypertension to the list?
Clearly an effective class of drug. What’s interesting is the hesitancy and often outright refusal of doctors to prescribe it. Exchange the diagnosis obesity for hypertension and it would be malpractice to withhold these medications. We have so many assumptions about people who are obese-undisciplined, uneducated, self indulgent etc.
Certainly impressive results. Long term studies will take decades; why the reluctance to treat patients long term with GLP-1 analogues ? No such reluctance to use long term anti hypertensives, insulin, antidepressants, etc. Seems still a stigma of obesity treatment. As if the “click” refers to an individual having the moral strength to change their eating habits rather than a physiologic event.
Agree that it's still a new drug and there will be unknown unknowns. Personally, I see myself being less enthusiastic with the incretin hormones e.g. loss of lean body mass. I am concerned seeing otherwise young and "healthy" people jump to glp1s, essentially committing to years/decades to long term usage. Side effects are a certainty with risk that increases with duration of exposure. On the flip side, I'm concerned about its use in the geriatric population also whose lean mass and strength is important, and using GLP1s may be counter productive. There is no free lunch.
I'd love to see Sensible Medicine engage more sensibly on the topic of obesity. The "click" you mention..... isn't it something like 5% of all dieters maintain their weight loss long term? That's a pretty small number of people. And most people who lose weight gain it back plus more. So, to the extent obesity is a problem it seems like a more reasonable treatment goal is weight maintenance rather than weight loss. Then you have to look at the pipeline from dieting to eating disorders, and weigh the real harms of eating disorders. Please please please bring Ragen Chastain (she writes Substack "Weight and Healthcare") to one of your panels for a discussion.
The “long term use” of any therapy will run into some of the same limitations you noted here: specifically, what happens after you exceed the follow up duration from the landmark trials? I suspect this concern will apply to nearly any medicine for any chronic condition. Statins, ACE inhibitors, beta blockers…DOACs….heck even ASA for secondary prevention…. Do you really know that the benefit persists even decades after initiation? No….and you can’t know, since it hasn’t been studied.
What does seem clear is that GLP-1 analogues do NOT have any legacy effect. But that’s not a knock against them…most drugs only work when you are actively taking them.
"What I mean is that patients that I have seen who have lost weight and maintained it with lifestyle change have something click." - This might be well worth understanding. The drugs have really altered some balance, perhaps forever.
This topic of GLP-1 Receptor Agonist also deserves its own Sensible Medicine podcast for the rampant obesity and diabetes epidemic we see in first world countries.
Why not take a further step back and ask yourself, the fact that people would rather take a pill than do basic activities, how fucking profoundly sick are we?
Coffin's already sealed, my friend. Doctors like you need to call it, and you probably won't because you're so entrenched.
1. Why do you assume it's not a durable effect? The trials of discontinuation that I'm familiar with were blinded, i.e. the patients didn't ever attempt to transition to "maintenance". I've had luck with many patients when they know they are going off the drug.
2. I take anti-hypertensives and they normalize my blood pressure. Should I be disappointed that there was no "click"? (I plan to take indefinitely).
3. Why is obesity somehow due to poor will power, but hypertension isn't? I suppose we're going back to treating alcohol use disorder as a defect of character, like obesity. Why can't we add diabetes and hypertension to the list?
Clearly an effective class of drug. What’s interesting is the hesitancy and often outright refusal of doctors to prescribe it. Exchange the diagnosis obesity for hypertension and it would be malpractice to withhold these medications. We have so many assumptions about people who are obese-undisciplined, uneducated, self indulgent etc.
Certainly impressive results. Long term studies will take decades; why the reluctance to treat patients long term with GLP-1 analogues ? No such reluctance to use long term anti hypertensives, insulin, antidepressants, etc. Seems still a stigma of obesity treatment. As if the “click” refers to an individual having the moral strength to change their eating habits rather than a physiologic event.