SURMOUNT-4: Weight regain despite continuing lifestyle and diet modifications

So here's the general idea:

I'm just going to make up arbitrary numbers and oversimplify for the case of illustration here. Let's say before GLPs, a level of 1 in your body happens when you haven't eaten in 3-6 hours and a level of 10 in your body happens when you just pigged out at the buffet and really got your money's worth. Your body is able to naturally vary the level between 0 and 20 just fine, but beyond that simply can't produce a level higher than that on its own.

You then start taking injections that knock your level up to 50, coming back down to 25 before the next shot. Over time you titrate up to higher doses and your levels are now fluctuating between 300 and 150.

When you stop taking injections, your body can't really do anything impactful for that particular hormone until the level comes back down under 20 again. That's going to be a while. Now hunger and fullness aren't handled by just one hormone and you'll still experience those sensations between meals due to other hormones and systems involved in the process. But you're not going to be "normal" again until that level degrades not just to 20, but likely another month later when it has degraded all the way down from 20 to 1.25. And even then, since these are complex systems, a few other things may need to fall into balance before hunger is fully "normal" again.

My point is we don’t know if the body will necessarily start making GLP-1 again, maybe not at month 2 maybe not at month 4. There is an assumption that we don’t have data on.

No one indicated they don’t understand half lives. 🙄

We know that testosterone supplementation depresses natural production. We know that BCP also suppresses natural production of hormones. In both cases, some systems have trouble bouncing back and returning to “normal.” Even after all the additions and their metabolites have long been processed out.

Why would GLP-1 be any different? Will it take 2 months, 6 months? There is no data.

The body doesn’t “do anything impactful” but IT IS IMPACTED. It has adjusted to life at 50 and the chemical rug is being pulled out. The person is going to feel like poop because they “feel” -25 because 50 became normal, the new zero. The body dgaf it just knows -25 or -50 sucks donkey balls, and that’s what it feels.

It’s called physical dependency. It’s different than addiction. And no the body won’t “do” anything to get back to 50, we already know that, that’s a meaningless measure.

My original point stands: going from a therapeutic dose to no dose instantly-without a taper-should be malpractice. There no reason to expect anything besides withdrawal and regain in these patients. These meds are tapered onto, it makes ALL the sense to taper off.
 
My point is we don’t know if the body will necessarily start making GLP-1 again, maybe not at month 2 maybe not at month 4. There is an assumption that we don’t have data on.

No one indicated they don’t understand half lives. 🙄

We know that testosterone supplementation depresses natural production. We know that BCP also suppresses natural production of hormones. In both cases, some systems have trouble bouncing back and returning to “normal.” Even after all the additions and their metabolites have long been processed out.

Why would GLP-1 be any different? Will it take 2 months, 6 months? There is no data.

The body doesn’t “do anything impactful” but IT IS IMPACTED. It has adjusted to life at 50 and the chemical rug is being pulled out. The person is going to feel like poop because they “feel” -25 because 50 became normal, the new zero. The body dgaf it just knows -25 or -50 sucks donkey balls, and that’s what it feels.

It’s called physical dependency. It’s different than addiction. And no the body won’t “do” anything to get back to 50, we already know that, that’s a meaningless measure.

My original point stands: going from a therapeutic dose to no dose instantly-without a taper-should be malpractice. There no reason to expect anything besides withdrawal and regain in these patients. These meds are tapered onto, it makes ALL the sense to taper off.

I was trying to give you a useful answer based on what you appeared to be referring to. Let's start over on this one. What's your reasoning for thinking that the body ever stopped making GLP-1 or that it would need to restart making it?

And are you referring to production of GLP-1 in the gut (the signal detected by the Vagal nerve) or are you referring to the production of GLP-1 in the brain (the signal your brain is weighting into deciding what kind of hunger signaling to give you)?
 
You cannot really say that studies just stopping GLP's were unethical. To get the drug approved you first have to prove it is safe and it works, and at least for the earlier studies it was not available yet outside the trials. It is a more valid question about later studies with placebo as the control arm, as opposed to some other drug instead, but to clearly see effects on things like heart disease and mortality , you really need those studies. And while those in the placebo arm are not being helped directly at the time, the knowledge generated will save many lives in the future, and possibly their own once it is available. Trials are not mainly for the benefit of the people in the trials, but for the knowledge they create. Ethics committees do have to approve trials, but it is more about not causing harm than maximising benefit to the trial participants.
 
I have tried every diet there is and always gained the weight back. So, it's not a surprise to me. On the other hand, here is what my weight loss and maintenance looks like 75 weeks in. I think I'll stick with the medicine for the rest of my life, thank you very much.View attachment 12478
I'm happy for you. I am only in my 4th mo th of serious healthy goals. I originally thought I could drop 50 lbs in 3 months like my coworker. My coworker was 5' 7" at 245 roided and 40 years old. He is moody mf'r but hard ass worker. He stopped everything and went Tirz. Ate clean and down 50 in three months. Me... down25 in 3.5 months and had zero muscle compared to coworker. Totally disappointed based of coworker but my mindset has changed. I wanted quick weight loss initially, but after three months my.goals have changed. I've been on Tirz compound and have lost weight, but my knee pain pain is the most benefit. At this point, pain gone, I am taking the the slow route on weight loss. I hope to reach my goal weight o. My retirement date 1.5 years in the future. Good bless you and all of your family!
 
I've already made peace with the fact that I'll be on a GLP1 for my forever. Not just for weight control, but because of all the ancillary benefits. I like the person I am now. I actually have control over food and my habits, not the other way around, and I'm not going to give that up. I've spent half my life trying to fight a losing battle. Been there, done that. I'm older, so it wasn't a hard decision.
 
I have tried every diet there is and always gained the weight back. So, it's not a surprise to me. On the other hand, here is what my weight loss and maintenance looks like 75 weeks in. I think I'll stick with the medicine for the rest of my life, thank you very much.View attachment 12478
Do you have the same " fear" as me that one day, the medication will stop to work on our body and we will have to look for something else for help?
 
I've already made peace with the fact that I'll be on a GLP1 for my forever. Not just for weight control, but because of all the ancillary benefits. I like the person I am now. I actually have control over food and my habits, not the other way around, and I'm not going to give that up. I've spent half my life trying to fight a losing battle. Been there, done that. I'm older, so it wasn't a hard decision.
This is the bess post ever!!! GLP1 help us to let " mental space" free of food noise, diet, training plan, meal prep, buying clothes who fit, etc. Its will be an eternal preoccupation, but we now have help to achieve goals. Thank you for that!
 
I have tried every diet there is and always gained the weight back. So, it's not a surprise to me. On the other hand, here is what my weight loss and maintenance looks like 75 weeks in. I think I'll stick with the medicine for the rest of my life, thank you very much.View attachment 12478
Another peptide GOD in my book...
 
I'm not even mad that I'm gonna be on a glp-1 for life. My previous options were "be fat for life" and "be obsessing about how much I want food for life, and also probably be fat." The fact that I have the OPTION of "take an inexpensive shot weekly for life" is a miracle.
 
Do you have the same " fear" as me that one day, the medication will stop to work on our body and we will have to look for something else for help?
Not really. We don't worry about exogenous testosterone not working anymore.
 
Do you have the same " fear" as me that one day, the medication will stop to work on our body and we will have to look for something else for help?

Fear not friend. There is endless money to be made and so the search for something else that works even better will never end. We'll all probably be on these for some period of time until something even better comes along. That is why I have a hard time stockpiling beyond 5-10 years worth.
 
Clearly, "remaining on the lifestyle interventions" was a lie. If someone could explain to me how someone could gain weight in a 500-calorie deficit and 150+ minutes a week of cardio, I would appreciate it.
THIS ☝️☝️☝️☝️☝️☝️☝️☝️☝️
 
A potential advantage of cagri over GLPs for maintaining weight after stopping (or going on a lower maintenance dose):

Gemini said:
Some researchers hypothesize that amylin analogues may be better at "resetting" the body’s adipostatic set point.

In obesity, the body becomes "leptin resistant"—it ignores the hormone that says "we have enough fat, stop eating." Most GLP-1s do not fix this; they simply bypass it.

The Amylin Fix: Preclinical and early Phase 3 data (REDEFINE program) show that amylin analogues sensitize the brain to leptin. By restoring this natural feedback loop, CagriSema may help the body maintain its own weight more effectively after the "chemical brake" of the medication is removed.
It could be Novo's best hope for their CagriSema having a competitive advantage over EL's tirz and reta, at least until EL's eloralintide gets to market.

OTOH, cagri slows the GI tract more than anything (that I can tell), so not ideal for me except at a low dose for a fiber-rich, plant-based diet.
 
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I have tried every diet there is and always gained the weight back. So, it's not a surprise to me. On the other hand, here is what my weight loss and maintenance looks like 75 weeks in. I think I'll stick with the medicine for the rest of my life, thank you very much.View attachment 12478
Preach.

I have had long successful periods of success, but that required unhealthy obsession disguised as discipline .

I love that I know how to manage my nutrition.

And I know how much easier it is to apply that information while on Reta.

Hit goal and microdose to maintain.
 
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