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I'm sorry I don't know how to link comment and I addressed this question above. It's a really good question, with very undefined answer.

That's a very good question. Unfortunately the answer is nearly undefined/very high variance depending on the person undergoing the weight loss. There's a huge range of expected outcomes depending on history and weight loss plan.

Ideal case might be Neutral LBM: Fairly obese youngish person. No training history (say someone that was super active, but not athletic, in HS). Goes to college, walks a ton stays pretty skinny. Gets first desk job around 25-26 and gains a ton of weight. Holds onto the weight, without much activity for 2-3 years. Diets in the most careful sense (.5% of bodyweight per week for 3-5 weeks then a maintenance week, macros on point, heavy resistance training, limited intense cardio). This person might stay LBM neutral, actually gain muscle and come out with massively improved body composition both on a naive DEXA scan and in reality.
Middling case might be Low LBM loss: Person has a decent training/life history, so they are carrying some "extra" muscle vs baseline. Been overweight for a while. Weight loss is limited to .5% bodyweight per week, with 2-3 cheat days per month (but no maintenance weeks). Resistance training is decent, limited cardio. They're going to lose some, LBM, might lose some muscle, but not too much. Exact numbers are hard, but would be reasonable to expect naive body composition to go way up (DEXA scan) and if you spent time carefully figuring out if they lost muscle/bone/other, it'd be mostly other (if not entirely other).
Pretty bad case might be High LBM loss: Average life/training history, person does intense cardio and aims for >1% bodyweight per week of weight loss. This person is going to get hit with a truck of LBM loss (absent pharmacological interventions or lucky genetics).

So the money question is where does Semaglutide stack up? We know from the paper that they didn't provide quality training advice, but we also know that the weight loss was spread (non-linearly) over 68 weeks (simple division meaning .22% per week, when .5% per week is seen as a very muscle/LBM preserving rec'd rate). I'm away from desktop so I don't have the study pulled up, but iirc the distribution of weight loss rates over time was very conservative/favorable to preserving muscle/LBM. We also know there was poor (if standard for diet research) compliance with the plans, b/c the weight loss average rate was much lower than expected for the diet advice that was provided.

This is why the results are concerning. If you told me someone was going to lose .5%-.7% per bodyweight per week for a month or two, then really slowly lose weight for the remainder of 68 weeks, and have professionally provided diet/training advice I would expect them to lose lower than average LBM. On the other hand, maybe it's an effect of being given a weight loss drug and seeing your weight drop? You think "heck this is awesome, I'm just going to chill and get skinny".

I don't know. But, the results combined with the reports of it making people "skinny fat" coming from multiple sources, notably largely consisting of doctors that have been giving it to people and then going sounding the alarm, adds another arrow to the bundle of "maybe we pump the breaks on this, or at least go into very very carefully with professional resistance training and a well craft diet" vs (what people seem to be doing (anecdotally) of pinning semaglutide once a week and chilling.

No disagreement from me :)

If you are interested in this drug to lose weight go very carefully. You might lose weight, but be plausibly more likely to get type 2 beetus at the end.

Not to my knowledge. There's a handful of studies that are pretty superficial (i.e. people come in for some DEXA (body composition) scans and that's it. I think it's going to take some time, because anyone involved in seeking approval of the drug has a huge negative incentive to look in this box, given the at least plausibly neutral results from the first supportive studies.

I think the place to look for citizen science on this is going to be in the longevity community and similar areas where you have people semi-openly experimenting with what is sometimes colloquially called "sports TRT" (i.e. running a testosterone only steroid cycle with modest amounts compared to other uses). Certainly a lot of people that hoped on the TRT optimization bandwagon in the last few years (telemedicine changes may have spurred this on as far as I can tell) are overweight, and I can't imagine they won't try another (sometimes insurance eligible) injectable to fix the overweight part. The data will be messy, but I think there will be hints in a few years.

Breaking my thoughts to your comment into 4 parts.

1: "Were you to follow your advice of "days of eating right, sleeping right and training for every single day of over eating" - which people who are obese have tried for decades and achieving normal BMI is rare - how is this mechanically different? Eating right means smaller meals and eating less kcals than daily metabolic needs"

All these using Freedom Units:

I've cut from >230 (I think peak around 245/250) to under 190 2 times with a 3rd 30 pound cut snuck in there. Going off Friday afternoon memory:
2013: >230 (Graduated law school, moved back to home state)
2014:<190 (insane caloric restriction combined with dumb resistance training and lots of cardio).
2015end:>230 (in 2015ish I started a new job with horrible commute, ~3 hours of driving a day).
2016end/2017/2019/part2020: <190 (keto/IF/less dumb lifting/working from home)
2020-2023: Long slow accumulation from 190 to >230 then down to just over 200, then back to 230 now down again. 505 squat(wraps)/405 deadlift/260 bench/190 ohp (all between 200-220 BW).

In 2020 I had 2 major life changes. My first (of now 2) kids was born and I decided to bulk, not realizing how much harder I would find it to lose weight when I had child induced sleep deprivation + ~5% of the free time I used to have (WFH 40-45 hours per week + and no kids = very high free time). The combination of intentional weight gain + sleep deprivation was/is brutal, and I'm still dealing with the aftermath.

Now I'm considering things and trying to cut (while maintaining muscle). So, I would say I have followed it and am back to following it. This is not the exhortation of some skinny s**t that's run a 5k a day for 20 years and never had any trouble with weight. This is from someone who has been to the (bottom? top?) of the mountain (stayed there) and is trying to get back.

Current systems seem crap. I've seen 3% able to to keep a significant bodyweight loss off for a year said in many places. I don't have an answer, other than I don't think the answer is Semaglutide. 

2: To the proposed Semaglutide/AADs stack (or sequential usage), I think that's a very intriguing idea if someone is in their 20s, has disposable income, goes into it both eyes open with blood testing, good sleep/diet/lifting/coaching and generally takes it seriously. Personally, I think it would be somewhat successful, if only because it would function as an very powerful compliance filter (i.e. if someone complies with all the blood testing to go on blast, and diet/sleep/lift/coaching they are going to see very good results regardless, but having the drugs will very plausibly help with compliance). I would note that going straight to Anavar seems a mite excessive, and well monitored "sports TRT" would seem a good first step if someone is thinking of this route (although I have heard in many places it is easier to get a bottle of Anavar than monitored "TRT" (I could more easily get a script for Deca + Test than reliably sourceAnavar based on my understanding)). Disclosure: Purely hypothetical for me, I've never experienced a lifting plateau that simple compliance with programming/sleep/diet didn't fix, so never felt it was reasonable to pursue assistance even before other concerns (i.e. 2 kids and a wife and just terrible genetics for drug interactions).

3: Mechanical stuff: No clue here at all. My honest shot in the dark is 3 guesses.
3a: Semaglutide (based on personal reports online) absolutely messes with your brain/general thought patterns. This could be downstream of hormone changes from dieting, or some unknown interaction or something else. If you go and read people's stories this is a very common theme. It's doing more things in your brain than messing with perceptions of fullness/hunger/slowing your stomach down.

3b: Hand wavey "the body is complicated" and who knows on nutrient abosoption/mechanisms.

3c:I think we are so far from understanding willpower (even as it relates to food) that our advice on this front is closer to mysticism than anything else. More honestly, I think we'd be better off simply telling people to do a modified 12 steps with food, or intentionally obsessing about clean eating (i.e. if you hit 30 and have been overweight for >5 years you're probably better off being an obsessed nutter that can't shut the f**k up about keto/vegan/carnivore and weighing a healthy BW + doing cardio than you are staying overweight)

4: "What do you think a hypothetical ASI system validated on results is going to prescribe in 2050? It's not going to be 1 pill once a day. You will likely need an implant loaded with hundreds of drugs and the doses are varying in response to feedback from implanted sensors."

Yes, strong agree (with the caveat I think you need to add at least another 50 years).

I've heard a lot of soccer leagues are taking steps to address headers, but afaik, it's a bit of a false lead b/c (and this is weak knowledge) a lot of the concussions are not header related. Happily, your kids didn't want to play it so doesn't matter much.

Boxing is such an odd sport in the modern context. I'd also add that you should be wary of some other MAs like TKD, as depending on the exact ruleset there can be an extreme focus on kicks to the head.

While I disagree, I can see why you would make that choice. Personally I stopped doing MAs when I realized I just really didn't like getting hit in the face.

Seems reasonable. I think the variance MA school to MA school is so incredibly high that it's almost impossible to layout a plan other than "visit schools within a reasonable trip and see".

Fair enough. Certainly schools have that, other schools have different cultures as well (but I'd guess the average is closer to your thought). Likely a different vibe from track/cross-country and marching band for sure. (Which isn't too say you don't have people that crossover/differences).

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