New 5 Receptor Agonist

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deleted.user.16 said:
30% on average maybe.

There are people in Retatrutide trials who only lost 5% of their weight after nearly a year on it. I'm sure they would appreciate another option!

Also for some people 30% might not be enough. What if your starting weight is 300lb+? You take Reta, stall at 210, maybe you'd want something stronger to get you to into the 100s.
Yup this is literally the issue I have now, my highest weight was around 360lbs and I started mounjaro/tirzepatide at 339.2lbs I'm currently around 266lbs after being on Mounjaro for a year.

I still have another 75lbs-85lbs to lose and I've switched to reta but it hasn't been very effective so far, I've not lost much weight and my appetite suppression isn't as good as it was on Mounjaro and I find I can eat a lot more before getting full with reta when compared with mounjaro.

There's definitely a large room for improvement in regards to weight loss drugs treating more severely obese such as myself.

I feel like the current landscape of weight loss drugs is more geared towards the overweight population rather than the obese/severely obese. Hopefully one of these pharmaceutical giants can create a tirzepatide/retatrutide for people like me who have to lose close to half of their body weight or more.
 
lessthanhalf said:
GLP drugs do actually fix a lot of the underlying metabolic problems , they reduce blood sugar, blood pressure, lipids and insulin resistance both as a direct action of the drugs themselves as well as secondary to the lost weight.

The problem with diet and exercise as a solution to obesity, however well optimised, is the long term. Maintaining that takes conscious cognitive effort or restraint, or at least nearly always, it is not impossible to turn those better health behaviors into new unconscious habits, but it is difficult and most people do not succeed. And the problem with cognitive effort as a strategy to fix a long term problem is that people just have limits on their resources of it, it just runs out eventually. It is mentally and physically tiring to maintain that effort, so sooner or later people revert to old patterns of behavior. And to be fair people with especially severe obesity are on average probably less good than average at maintaining healthy eating patterns and exercise, no doubt part of the reason they became obese. This is not a moral failing , it is just part of normal variation in people, plus an obesogenic environment, and once obesity sets in, it becomes harder to exercise, and the appetite regulation system starts to progressively malfunction as hormonal and neurotransmitter regulatory systems fail to function correctly under the metabolic stress of obesity.

Prior to the availability of GLP drugs long term weight loss of 5% or more rarely 10% was considered a great success in diet and exercise based therapy for obesity, as this small loss does significantly reduce long term health consequences. All the evidence I have ever seen is that any intervention short of surgery for weight loss, fails in the long term with nearly everyone putting the weight back on eventually after the intervention ceases, and maintaining any intervention in the long term runs into the cognitive effort or cognitive restraint problem .

GLP drugs completely bypass the cognitive effort issue as one injection a week is not exactly hard compared to sticking to a 1600 or 1800 calorie diet long term, and in the long term they just keep on working so long as you keep taking them. I think the evidence seen in the studies and on this forum provide good evidence of their effectiveness and that it is maintained long term. Better diet and exercise is important, but people taking GLP drugs for obesity without any special effort put into lifestyle changes lose weight anyway. And there is evidence that GLP drugs improve people's food choices, and just from personal experience it is much easier to exercise at normal or near normal weights than when severely obese.

My opinion is that diet and exercise are a largely ineffective therapy for obesity, based on long term results from thousands of studies over decades, not completely useless or pointless, but with very poor long term success rates. GLP drugs just work, except for a few who get bad side effects, or who respond poorly to them. But for the large majority they enable significant weight loss of 10-30% long term, with added bonus health benefits.
I am 💯 aligned with a lot of what you said, especially around how hard long term weight loss is and how much GLP meds help with appetite and adherence. For most people.... they’re a game changer.

And yes, they absolutely improve things like blood sugar, insulin resistance, and lipids, both directly and from the weight loss.

But I think it goes too far to say they basically replace the need for lifestyle or that diet and exercise are mostly ineffective.

Even with something like Reta or other GLP based meds, they’re not fully correcting the underlying system, they’re helping regulate it. That’s a big difference.

The “people regain weight” piece is real, but a lot of that comes from how people were doing it in the first place. Chronic under eating, no resistance training, losing a lot of lean mass, and not adjusting intake as they go. That sets people up to regain.

Muscle is one of the biggest drivers of metabolic rate and glucose disposal. If you're not protecting it and even changing it, the result is an even slower metabolic rate, making plateaus more likely, and making regain easier later on.

Strength training three times a week is not optional if you care about insulin sensitivity, bone density, testosterone tone, and your ability to be physically powerful in your 60s and 70s.

So it’s not just about losing weight, it’s about what kind of weight you’re losing, and what your metabolic health looks like at the end. Muscle is not aethetic, it is metabolic currency.

When you actually support the medication properly with enough protein, resistance training, and not driving calories too low, you’re not just losing weight, you’re changing that very foundation in a way that’s more sustainable. The med can't do that alone.

So, the idea that meds completely bypass effort isn’t totally true. They lower the barrier, for sure, but people still plateau, people still lose more muscle than they should, and people still regain if nothing else changes and the med is stopped.... Or even if it isn't.

So I don’t really see it as meds vs lifestyle.

It’s more that the meds make it possible for lifestyle changes to actually stick, especially for people who’ve struggled for years. But how far someone goes and how well they maintain still depends a lot on what they do alongside it.
 
cheaperseeker said:
Did you talk to a lawyer? An MRI or something might be able to prove what he did.
I did. The problem is that some people’s small intestine grows longer postoperative- so his attorney could claim that it just grew in the time after surgery. I don’t think mine has- I don’t think my revised stomach got bigger either, because if I eat 1 bite too much rice? I’m going to regret the heck out of it and probably puke. Rice and bread swell tremendously, I guess.

I actually knew a man who was revised 3 times because his body kept lengthening his small intestine. I was starting to wonder if he was part starfish.
 
cheaperseeker said:
I think it's both. The cognitive load is the symptom and endocrine dysfunction is the underlying cause. The hormones were telling us we were starving, even when we already had more than enough nutrition. GLPs hit what diet and exercise can't.
I have never had food noise. I had no issues with overeating post surgical gastric reduction. I never craved sweets. I crave strange stuff like liver or steak or fish. I lost weight first with an intestinal bypass, now with glps. I was put on restrictive diets starting at age 8, and my sister used to tell people that she was glad she didn’t need to diet because she didn’t have my willpower. So yes, it may be both for some, but not all.

And yes, I was always active. I played softball and swam competitively in grade school, played soccer JV in high school and college and lifted weights the entire time I was on teams. Even now I’m more active than most of my friends and I feel like I’m a slug compared to when I was younger. I’ve always had muscle.
 
I remember reading that there's a bunch of research around the 4- and/or 5-receptor agonist offerings that hope to reduce/eliminate muscle loss issues associated with the current GLP1 offerings. Time will tell the tale.
 
I think the interesting agonist out of the 2 new ones is the one that Lily were working on in a separate stream for a standalone drug, was the one that stops the body going after muscle on a deficit. I know a lot of people struggle getting enough protein in during weight loss with GLP's, which is predominant factor in doing it, to help prevent against muscle loss.
 
The thing I wonder is if the Pharma companies have something they are already testing and spending money on, what is their incentive to look into something better. Are they going to come out with a new better product before making the money on the current product they spent so much money testing. Not sure of the answer to that.
 
Peotidethrowaway said:
How long before this hits the grey market I wonder
Takes a few morally grey area interested venture capitalists and either a vendor who can get hold of it. Or a alibaba compounder who will make you anything short of quailudes. Same with anyone who prison purses a couple vials of trevogrumab and garetasumab off to china. im totally kidding dont take this seriously do not do anything i just said
 
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