A New 5 Receptor Agonist

Beardboost said:

I doubt it will make it anywhere near trial approval — the danger profile is just too large. Amylin slows digestion down even further, wipes out cravings (that part is good) and leaves you feeling stuffed for hours on end, which raises the odds of heart burn, plus you end up eating far below what your body actually needs to stay healthy. Then Calcitonin enters the picture and cuts the brain off entirely from hunger signals. When GLP-1's help with weight loss and mental health, I'm all for them, but I strongly believe in pairing any GLP with real lifestyle changes — planning meals, eating on a steady schedule, building habits you can actually sustain so the weight stays off. Shutting hunger out of the mind completely while cutting food intake is a wrecking ball waiting to happen.
A number of members here are already, in practice, using a very close combination: reta along with cagrilintide, and for them it has been working rather effectively.

One clear situation in which GLP drugs deliver weaker weight loss results is among diabetics. Even when blood sugar control is excellent, the pounds shed tend to be noticeably lower than what non diabetics experience, which is why weight loss trials are run separately for those two populations. That makes diabetics another group who might gain from improved GLP options.

I would like to hear how severe the obesity is that Beardboost is addressing through GLP's alongside lifestyle, diet and exercise. The view that GLP's play only a modest role in the overall solution tends to come from individuals who are not dealing with severe obesity. If my guess about where this poster is coming from is mistaken, please set me straight.

Among people whose obesity is more severe, many have devoted decades to losing and keeping off weight through diet, exercise and lifestyle changes, only for those efforts to work at best temporarily. For them, GLP medications are the answer. They also make subsequent adjustments to lifestyle, diet and exercise simpler and easier to sustain. Those things are not meaningless, but decades of personal experience and a large body of scientific research indicate they mostly fail to produce or hold onto substantial weight loss, apart from a fortunate or unusually determined minority. GLP medications, by contrast, show strong success rates, though not universally, and keep that weight off over the long term as long as the medication is continued.
 
Lovedog100 said:

On a personal level, improved weight loss medications are something I'm eager to see. Before this even becomes available, I'll already have reached my target. The man in the video was difficult for me to take seriously. Between his very fat face and his extremely puffy hands, I simply can't see him as a credible voice on weight loss. I stopped watching partway through.



Given the profits that weight loss drugs bring in, along with people consuming processed foods in record quantities, additional drugs and protocols reaching the market seems likely. Funding will keep pouring into R&D, and into the products those companies turn out. Even before GLP's, weight loss was already a Billion dollar industry. Books, classes, gyms, drugs, companies such as weight watchers, healthy food delivery services, home exercise equipment — there was no shortage of ways for us to part with our money. For every fat person, a weekly pill or shot is the ultimate fantasy.

My cat is curled up on my lap right now, and I'm laughing so hard while trying not to jostle him. Hearing "your face is so fat, and your hands so puffy" aimed at me would leave me in tears. Honestly, I wish my list of people I can't stand were longer, because wow.
 
IvanD said:

For the people this is aimed at, it's a thrilling development, but in my view a triple agonist deserves more extensive research before we jump to five. We're in a marathon here, not a sprint, and at times I feel the medical field rushes ahead because of financial incentives or branding.

That's just my two cents.
No need to fret — Lilly has roughly a dozen retatrutide trials in the pipeline, and those should support prescribing it across a range of metabolic conditions.
 
Hoping Costco puts this combo pack on shelves soon!
0eea40938aea65ae70640a1c4b91f4a8ea96f9fabd2790fbe5af74c66e9a6184.webp


RFK, please make it happen!
 
Peotidethrowaway said:

I'm curious how soon this will show up on the grey market
Once production begins for human trials, my guess is the compound will inevitably find its way out and get replicated in a particular country.
 
Vash_ said:

Seriously, why bother? Reta has already been demonstrated to reduce body weight by 30% in people. That alone is absurd. Who actually requires a treatment that works even better?
For the version of me that once weighed 600lb, that wouldn't be too bad, and holding on to the majority of muscle would be a plus. We're getting nearer to options that could assist wheelchair users and older individuals, which would be a positive development.
 
lessthanhalf said:

Beardboost said:

I doubt it will make it anywhere near trial approval — the danger profile is just too large. Amylin slows digestion down even further, wipes out cravings (that part is good) and leaves you feeling stuffed for hours on end, which raises the odds of heart burn, plus you end up eating far below what your body actually needs to stay healthy. Then Calcitonin enters the picture and cuts the brain off entirely from hunger signals. When GLP-1's help with weight loss and mental health, I'm all for them, but I strongly believe in pairing any GLP with real lifestyle changes — planning meals, eating on a steady schedule, building habits you can actually sustain so the weight stays off. Shutting hunger out of the mind completely while cutting food intake is a wrecking ball waiting to happen.
A number of members here are already, in practice, using a very close combination: reta along with cagrilintide, and for them it has been working rather effectively.

One clear situation in which GLP drugs deliver weaker weight loss results is among diabetics. Even when blood sugar control is excellent, the pounds shed tend to be noticeably lower than what non diabetics experience, which is why weight loss trials are run separately for those two populations. That makes diabetics another group who might gain from improved GLP options.

I would like to hear how severe the obesity is that Beardboost is addressing through GLP's alongside lifestyle, diet and exercise. The view that GLP's play only a modest role in the overall solution tends to come from individuals who are not dealing with severe obesity. If my guess about where this poster is coming from is mistaken, please set me straight.

Among people whose obesity is more severe, many have devoted decades to losing and keeping off weight through diet, exercise and lifestyle changes, only for those efforts to work at best temporarily. For them, GLP medications are the answer. They also make subsequent adjustments to lifestyle, diet and exercise simpler and easier to sustain. Those things are not meaningless, but decades of personal experience and a large body of scientific research indicate they mostly fail to produce or hold onto substantial weight loss, apart from a fortunate or unusually determined minority. GLP medications, by contrast, show strong success rates, though not universally, and keep that weight off over the long term as long as the medication is continued.
There’s a chunk of your argument I’m on board with, particularly when it comes to severe obesity. For many individuals, medication ends up being the first intervention that delivers lasting results after years of cycling through every other option.

And the distinction between diabetic and non diabetic outcomes is real, that part isn’t up for debate.

Where I’d push back is the idea that meds are the answer and that for this group, everything else barely moves the needle.

Take something like Retaor stacked with Cagri. What the drug is doing is altering appetite, satiety, and how glucose is processed. The fundamental physiology underneath isn’t being swapped out.

When someone has severe obesity, those deeper drivers tend to be louder, not quieter. Insulin runs higher, metabolic adaptation is greater, and the body fights weight loss harder. A more potent medication doesn’t erase any of that.

On top of that, plenty of people have tried diet and exercise, but not in a form that protects muscle, keeps metabolism supported, or can be maintained over time. Years of undereating plus cardio is a totally different animal from eating enough, making protein a priority, and lifting weights consistently.

Do the meds make all of that more manageable? 100%. But those behaviors still shape how far a person gets and whether progress grinds to a halt.

So framing it as meds against lifestyle doesn’t fit for me.

What’s really happening is that the meds finally let lifestyle changes do what they were always meant to do.
 
Neptide said:

CNCCurrency said:

Came across this earlier today — pretty intriguing. In this matchup, reta will end up being the underdog.

View: https://www.youtube.com/watch?v=hZnjS9s6-JY
Maybe having additional competing drugs and a wider range of choices could push pricing lower.
If it ends up classified as a biologic, that outcome is pretty improbable. In that scenario, Lilly would hold the sole position as an authorized manufacturer, which would shut out compounding pharmacies entirely. On top of that, the patent would be stretched out over a much longer period, keeping their profit margins protected for an extended time. Naturally, the grey market would carry on regardless.
 
Having more options is a good thing, particularly when the newer ones come with fewer adverse effects (think the shift from Sema to Tirz).

Personally, Reta feels like a step backward — whatever that glucagon does, it sends my adrenalin/anxiety through the roof, or at least something like that; I honestly can't pin it down, but sleep is impossible.

On top of that, you could have 2 drugs that are each triple or quintuple agonists yet carry a different "weight" on every receptor... which would produce a completely distinct outcome.
 
Jfrick11 said:

lessthanhalf said:

Beardboost said:

I doubt it will make it anywhere near trial approval — the danger profile is just too large. Amylin slows digestion down even further, wipes out cravings (that part is good) and leaves you feeling stuffed for hours on end, which raises the odds of heart burn, plus you end up eating far below what your body actually needs to stay healthy. Then Calcitonin enters the picture and cuts the brain off entirely from hunger signals. When GLP-1's help with weight loss and mental health, I'm all for them, but I strongly believe in pairing any GLP with real lifestyle changes — planning meals, eating on a steady schedule, building habits you can actually sustain so the weight stays off. Shutting hunger out of the mind completely while cutting food intake is a wrecking ball waiting to happen.
A number of members here are already, in practice, using a very close combination: reta along with cagrilintide, and for them it has been working rather effectively.

One clear situation in which GLP drugs deliver weaker weight loss results is among diabetics. Even when blood sugar control is excellent, the pounds shed tend to be noticeably lower than what non diabetics experience, which is why weight loss trials are run separately for those two populations. That makes diabetics another group who might gain from improved GLP options.

I would like to hear how severe the obesity is that Beardboost is addressing through GLP's alongside lifestyle, diet and exercise. The view that GLP's play only a modest role in the overall solution tends to come from individuals who are not dealing with severe obesity. If my guess about where this poster is coming from is mistaken, please set me straight.

Among people whose obesity is more severe, many have devoted decades to losing and keeping off weight through diet, exercise and lifestyle changes, only for those efforts to work at best temporarily. For them, GLP medications are the answer. They also make subsequent adjustments to lifestyle, diet and exercise simpler and easier to sustain. Those things are not meaningless, but decades of personal experience and a large body of scientific research indicate they mostly fail to produce or hold onto substantial weight loss, apart from a fortunate or unusually determined minority. GLP medications, by contrast, show strong success rates, though not universally, and keep that weight off over the long term as long as the medication is continued.
There’s a chunk of your argument I’m on board with, particularly when it comes to severe obesity. For many individuals, medication ends up being the first intervention that delivers lasting results after years of cycling through every other option.

And the distinction between diabetic and non diabetic outcomes is real, that part isn’t up for debate.

Where I’d push back is the idea that meds are the answer and that for this group, everything else barely moves the needle.

Take something like Retaor stacked with Cagri. What the drug is doing is altering appetite, satiety, and how glucose is processed. The fundamental physiology underneath isn’t being swapped out.

When someone has severe obesity, those deeper drivers tend to be louder, not quieter. Insulin runs higher, metabolic adaptation is greater, and the body fights weight loss harder. A more potent medication doesn’t erase any of that.

On top of that, plenty of people have tried diet and exercise, but not in a form that protects muscle, keeps metabolism supported, or can be maintained over time. Years of undereating plus cardio is a totally different animal from eating enough, making protein a priority, and lifting weights consistently.

Do the meds make all of that more manageable? 100%. But those behaviors still shape how far a person gets and whether progress grinds to a halt.

So framing it as meds against lifestyle doesn’t fit for me.

What’s really happening is that the meds finally let lifestyle changes do what they were always meant to do.
GLP medications genuinely address many of the metabolic issues underneath: they lower blood sugar, blood pressure, lipids and insulin resistance, partly through direct drug action and partly because of the weight that gets lost.

When diet and exercise are used as the answer to obesity, even in a highly optimized form, the difficulty lies in the long run. Sustaining that requires deliberate mental effort or restraint, or at least almost always does; turning improved health behaviors into automatic habits is not impossible, but it is hard and most people fail to do it. And the trouble with relying on cognitive effort to solve a long-term problem is that people simply have finite reserves of it, and those reserves eventually run dry. Keeping up that effort is draining both mentally and physically, so eventually old behavior patterns return. To be fair, people with particularly severe obesity are on average probably worse than average at sticking with healthy eating and exercise, which is undoubtedly part of why they became obese. That is not a moral failure; it is just normal human variation, combined with an obesogenic environment, and once obesity develops, exercising becomes harder, and the appetite regulation system begins to progressively malfunction as hormonal and neurotransmitter regulatory systems stop working correctly under the metabolic stress of obesity.

Before GLP drugs existed, long-term weight loss of 5% or more, and rarely 10%, was regarded as a major success in diet-and-exercise treatment for obesity, since even this modest loss substantially lowers long-term health consequences. Everything I have ever seen indicates that any weight-loss intervention short of surgery fails over the long term, with nearly everyone regaining the weight eventually after the intervention stops, and sustaining any intervention long term runs straight into the cognitive effort or cognitive restraint problem.

GLP drugs sidestep the cognitive effort problem entirely, because 1 injection per week is not exactly difficult compared with adhering to a 1600 or 1800 calorie diet long term, and over time they simply keep working as long as you keep taking them. In my view, the evidence from the studies and on this forum demonstrates their effectiveness well, and shows that it is maintained long term. Better diet and exercise matter, but people who take GLP drugs for obesity without making any special lifestyle effort still lose weight. There is also evidence that GLP drugs improve people's food choices, and from personal experience it is far easier to exercise at normal or near-normal weights than when severely obese.

My position is that diet and exercise are a largely ineffective therapy for obesity, judging by long-term results from thousands of studies across decades: not completely useless or pointless, but with very poor long-term success rates. GLP drugs simply work, aside from a few people who get bad side effects or respond poorly to them. For the large majority, though, they enable significant long-term weight loss of 10-30%, with extra health benefits as a bonus.
 
lessthanhalf said:

Jfrick11 said:

lessthanhalf said:

Beardboost said:

I doubt it will make it anywhere near trial approval — the danger profile is just too large. Amylin slows digestion down even further, wipes out cravings (that part is good) and leaves you feeling stuffed for hours on end, which raises the odds of heart burn, plus you end up eating far below what your body actually needs to stay healthy. Then Calcitonin enters the picture and cuts the brain off entirely from hunger signals. When GLP-1's help with weight loss and mental health, I'm all for them, but I strongly believe in pairing any GLP with real lifestyle changes — planning meals, eating on a steady schedule, building habits you can actually sustain so the weight stays off. Shutting hunger out of the mind completely while cutting food intake is a wrecking ball waiting to happen.
A number of members here are already, in practice, using a very close combination: reta along with cagrilintide, and for them it has been working rather effectively.

One clear situation in which GLP drugs deliver weaker weight loss results is among diabetics. Even when blood sugar control is excellent, the pounds shed tend to be noticeably lower than what non diabetics experience, which is why weight loss trials are run separately for those two populations. That makes diabetics another group who might gain from improved GLP options.

I would like to hear how severe the obesity is that Beardboost is addressing through GLP's alongside lifestyle, diet and exercise. The view that GLP's play only a modest role in the overall solution tends to come from individuals who are not dealing with severe obesity. If my guess about where this poster is coming from is mistaken, please set me straight.

Among people whose obesity is more severe, many have devoted decades to losing and keeping off weight through diet, exercise and lifestyle changes, only for those efforts to work at best temporarily. For them, GLP medications are the answer. They also make subsequent adjustments to lifestyle, diet and exercise simpler and easier to sustain. Those things are not meaningless, but decades of personal experience and a large body of scientific research indicate they mostly fail to produce or hold onto substantial weight loss, apart from a fortunate or unusually determined minority. GLP medications, by contrast, show strong success rates, though not universally, and keep that weight off over the long term as long as the medication is continued.
There’s a chunk of your argument I’m on board with, particularly when it comes to severe obesity. For many individuals, medication ends up being the first intervention that delivers lasting results after years of cycling through every other option.

And the distinction between diabetic and non diabetic outcomes is real, that part isn’t up for debate.

Where I’d push back is the idea that meds are the answer and that for this group, everything else barely moves the needle.

Take something like Retaor stacked with Cagri. What the drug is doing is altering appetite, satiety, and how glucose is processed. The fundamental physiology underneath isn’t being swapped out.

When someone has severe obesity, those deeper drivers tend to be louder, not quieter. Insulin runs higher, metabolic adaptation is greater, and the body fights weight loss harder. A more potent medication doesn’t erase any of that.

On top of that, plenty of people have tried diet and exercise, but not in a form that protects muscle, keeps metabolism supported, or can be maintained over time. Years of undereating plus cardio is a totally different animal from eating enough, making protein a priority, and lifting weights consistently.

Do the meds make all of that more manageable? 100%. But those behaviors still shape how far a person gets and whether progress grinds to a halt.

So framing it as meds against lifestyle doesn’t fit for me.

What’s really happening is that the meds finally let lifestyle changes do what they were always meant to do.
GLP medications genuinely address many of the metabolic issues underneath: they lower blood sugar, blood pressure, lipids and insulin resistance, partly through direct drug action and partly because of the weight that gets lost.

When diet and exercise are used as the answer to obesity, even in a highly optimized form, the difficulty lies in the long run. Sustaining that requires deliberate mental effort or restraint, or at least almost always does; turning improved health behaviors into automatic habits is not impossible, but it is hard and most people fail to do it. And the trouble with relying on cognitive effort to solve a long-term problem is that people simply have finite reserves of it, and those reserves eventually run dry. Keeping up that effort is draining both mentally and physically, so eventually old behavior patterns return. To be fair, people with particularly severe obesity are on average probably worse than average at sticking with healthy eating and exercise, which is undoubtedly part of why they became obese. That is not a moral failure; it is just normal human variation, combined with an obesogenic environment, and once obesity develops, exercising becomes harder, and the appetite regulation system begins to progressively malfunction as hormonal and neurotransmitter regulatory systems stop working correctly under the metabolic stress of obesity.

Before GLP drugs existed, long-term weight loss of 5% or more, and rarely 10%, was regarded as a major success in diet-and-exercise treatment for obesity, since even this modest loss substantially lowers long-term health consequences. Everything I have ever seen indicates that any weight-loss intervention short of surgery fails over the long term, with nearly everyone regaining the weight eventually after the intervention stops, and sustaining any intervention long term runs straight into the cognitive effort or cognitive restraint problem.

GLP drugs sidestep the cognitive effort problem entirely, because 1 injection per week is not exactly difficult compared with adhering to a 1600 or 1800 calorie diet long term, and over time they simply keep working as long as you keep taking them. In my view, the evidence from the studies and on this forum demonstrates their effectiveness well, and shows that it is maintained long term. Better diet and exercise matter, but people who take GLP drugs for obesity without making any special lifestyle effort still lose weight. There is also evidence that GLP drugs improve people's food choices, and from personal experience it is far easier to exercise at normal or near-normal weights than when severely obese.

My position is that diet and exercise are a largely ineffective therapy for obesity, judging by long-term results from thousands of studies across decades: not completely useless or pointless, but with very poor long-term success rates. GLP drugs simply work, aside from a few people who get bad side effects or respond poorly to them. For the large majority, though, they enable significant long-term weight loss of 10-30%, with extra health benefits as a bonus.
100% with you. Constantly thinking about food, every single day - what's on your plate, what's coming next, which tactics you'll rely on at holiday gatherings, logging everything, fighting the urge to keep eating once you've reached your limit while your body insists you're still hungry, how to resist the donuts a coworker brought in when you're stressed and hungry, and so on - that's an enormous mental burden, and for the majority of people it simply can't be sustained for a lifetime.

I also know a handful of people who went through the surgery and ended up regaining the weight anyway.
 
cheaperseeker said:

lessthanhalf said:

Jfrick11 said:

lessthanhalf said:

Beardboost said:

I doubt it will make it anywhere near trial approval — the danger profile is just too large. Amylin slows digestion down even further, wipes out cravings (that part is good) and leaves you feeling stuffed for hours on end, which raises the odds of heart burn, plus you end up eating far below what your body actually needs to stay healthy. Then Calcitonin enters the picture and cuts the brain off entirely from hunger signals. When GLP-1's help with weight loss and mental health, I'm all for them, but I strongly believe in pairing any GLP with real lifestyle changes — planning meals, eating on a steady schedule, building habits you can actually sustain so the weight stays off. Shutting hunger out of the mind completely while cutting food intake is a wrecking ball waiting to happen.
A number of members here are already, in practice, using a very close combination: reta along with cagrilintide, and for them it has been working rather effectively.

One clear situation in which GLP drugs deliver weaker weight loss results is among diabetics. Even when blood sugar control is excellent, the pounds shed tend to be noticeably lower than what non diabetics experience, which is why weight loss trials are run separately for those two populations. That makes diabetics another group who might gain from improved GLP options.

I would like to hear how severe the obesity is that Beardboost is addressing through GLP's alongside lifestyle, diet and exercise. The view that GLP's play only a modest role in the overall solution tends to come from individuals who are not dealing with severe obesity. If my guess about where this poster is coming from is mistaken, please set me straight.

Among people whose obesity is more severe, many have devoted decades to losing and keeping off weight through diet, exercise and lifestyle changes, only for those efforts to work at best temporarily. For them, GLP medications are the answer. They also make subsequent adjustments to lifestyle, diet and exercise simpler and easier to sustain. Those things are not meaningless, but decades of personal experience and a large body of scientific research indicate they mostly fail to produce or hold onto substantial weight loss, apart from a fortunate or unusually determined minority. GLP medications, by contrast, show strong success rates, though not universally, and keep that weight off over the long term as long as the medication is continued.
There’s a chunk of your argument I’m on board with, particularly when it comes to severe obesity. For many individuals, medication ends up being the first intervention that delivers lasting results after years of cycling through every other option.

And the distinction between diabetic and non diabetic outcomes is real, that part isn’t up for debate.

Where I’d push back is the idea that meds are the answer and that for this group, everything else barely moves the needle.

Take something like Retaor stacked with Cagri. What the drug is doing is altering appetite, satiety, and how glucose is processed. The fundamental physiology underneath isn’t being swapped out.

When someone has severe obesity, those deeper drivers tend to be louder, not quieter. Insulin runs higher, metabolic adaptation is greater, and the body fights weight loss harder. A more potent medication doesn’t erase any of that.

On top of that, plenty of people have tried diet and exercise, but not in a form that protects muscle, keeps metabolism supported, or can be maintained over time. Years of undereating plus cardio is a totally different animal from eating enough, making protein a priority, and lifting weights consistently.

Do the meds make all of that more manageable? 100%. But those behaviors still shape how far a person gets and whether progress grinds to a halt.

So framing it as meds against lifestyle doesn’t fit for me.

What’s really happening is that the meds finally let lifestyle changes do what they were always meant to do.
GLP medications genuinely address many of the metabolic issues underneath: they lower blood sugar, blood pressure, lipids and insulin resistance, partly through direct drug action and partly because of the weight that gets lost.

When diet and exercise are used as the answer to obesity, even in a highly optimized form, the difficulty lies in the long run. Sustaining that requires deliberate mental effort or restraint, or at least almost always does; turning improved health behaviors into automatic habits is not impossible, but it is hard and most people fail to do it. And the trouble with relying on cognitive effort to solve a long-term problem is that people simply have finite reserves of it, and those reserves eventually run dry. Keeping up that effort is draining both mentally and physically, so eventually old behavior patterns return. To be fair, people with particularly severe obesity are on average probably worse than average at sticking with healthy eating and exercise, which is undoubtedly part of why they became obese. That is not a moral failure; it is just normal human variation, combined with an obesogenic environment, and once obesity develops, exercising becomes harder, and the appetite regulation system begins to progressively malfunction as hormonal and neurotransmitter regulatory systems stop working correctly under the metabolic stress of obesity.

Before GLP drugs existed, long-term weight loss of 5% or more, and rarely 10%, was regarded as a major success in diet-and-exercise treatment for obesity, since even this modest loss substantially lowers long-term health consequences. Everything I have ever seen indicates that any weight-loss intervention short of surgery fails over the long term, with nearly everyone regaining the weight eventually after the intervention stops, and sustaining any intervention long term runs straight into the cognitive effort or cognitive restraint problem.

GLP drugs sidestep the cognitive effort problem entirely, because 1 injection per week is not exactly difficult compared with adhering to a 1600 or 1800 calorie diet long term, and over time they simply keep working as long as you keep taking them. In my view, the evidence from the studies and on this forum demonstrates their effectiveness well, and shows that it is maintained long term. Better diet and exercise matter, but people who take GLP drugs for obesity without making any special lifestyle effort still lose weight. There is also evidence that GLP drugs improve people's food choices, and from personal experience it is far easier to exercise at normal or near-normal weights than when severely obese.

My position is that diet and exercise are a largely ineffective therapy for obesity, judging by long-term results from thousands of studies across decades: not completely useless or pointless, but with very poor long-term success rates. GLP drugs simply work, aside from a few people who get bad side effects or respond poorly to them. For the large majority, though, they enable significant long-term weight loss of 10-30%, with extra health benefits as a bonus.
100% with you. Constantly thinking about food, every single day - what's on your plate, what's coming next, which tactics you'll rely on at holiday gatherings, logging everything, fighting the urge to keep eating once you've reached your limit while your body insists you're still hungry, how to resist the donuts a coworker brought in when you're stressed and hungry, and so on - that's an enormous mental burden, and for the majority of people it simply can't be sustained for a lifetime.

I also know a handful of people who went through the surgery and ended up regaining the weight anyway.
The operation I'd been cleared for was altered by my surgeon. He never put the changes in writing — in effect, my operative report was falsified regarding what he actually did. He only came clean to me once my weight loss halted, after roughly 110 lbs had come off, and after I'd already spent time working with his office to figure out the cause of the stall. When he finally admitted it, I asked when the revision I'd paid for would happen. He told me he didn't believe in revisions, and that I counted as a statistical success since I'd dropped over 100 lbs. I had no way out. Still severely obese. Proving anything was impossible, because his admission came by phone, not on paper. Nothing helped until GLPs. I'll stay on them for the rest of my life.
 
FlowerFairy said:

cheaperseeker said:

lessthanhalf said:

Jfrick11 said:

lessthanhalf said:

Beardboost said:

I doubt it will make it anywhere near trial approval — the danger profile is just too large. Amylin slows digestion down even further, wipes out cravings (that part is good) and leaves you feeling stuffed for hours on end, which raises the odds of heart burn, plus you end up eating far below what your body actually needs to stay healthy. Then Calcitonin enters the picture and cuts the brain off entirely from hunger signals. When GLP-1's help with weight loss and mental health, I'm all for them, but I strongly believe in pairing any GLP with real lifestyle changes — planning meals, eating on a steady schedule, building habits you can actually sustain so the weight stays off. Shutting hunger out of the mind completely while cutting food intake is a wrecking ball waiting to happen.
A number of members here are already, in practice, using a very close combination: reta along with cagrilintide, and for them it has been working rather effectively.

One clear situation in which GLP drugs deliver weaker weight loss results is among diabetics. Even when blood sugar control is excellent, the pounds shed tend to be noticeably lower than what non diabetics experience, which is why weight loss trials are run separately for those two populations. That makes diabetics another group who might gain from improved GLP options.

I would like to hear how severe the obesity is that Beardboost is addressing through GLP's alongside lifestyle, diet and exercise. The view that GLP's play only a modest role in the overall solution tends to come from individuals who are not dealing with severe obesity. If my guess about where this poster is coming from is mistaken, please set me straight.

Among people whose obesity is more severe, many have devoted decades to losing and keeping off weight through diet, exercise and lifestyle changes, only for those efforts to work at best temporarily. For them, GLP medications are the answer. They also make subsequent adjustments to lifestyle, diet and exercise simpler and easier to sustain. Those things are not meaningless, but decades of personal experience and a large body of scientific research indicate they mostly fail to produce or hold onto substantial weight loss, apart from a fortunate or unusually determined minority. GLP medications, by contrast, show strong success rates, though not universally, and keep that weight off over the long term as long as the medication is continued.
There’s a chunk of your argument I’m on board with, particularly when it comes to severe obesity. For many individuals, medication ends up being the first intervention that delivers lasting results after years of cycling through every other option.

And the distinction between diabetic and non diabetic outcomes is real, that part isn’t up for debate.

Where I’d push back is the idea that meds are the answer and that for this group, everything else barely moves the needle.

Take something like Retaor stacked with Cagri. What the drug is doing is altering appetite, satiety, and how glucose is processed. The fundamental physiology underneath isn’t being swapped out.

When someone has severe obesity, those deeper drivers tend to be louder, not quieter. Insulin runs higher, metabolic adaptation is greater, and the body fights weight loss harder. A more potent medication doesn’t erase any of that.

On top of that, plenty of people have tried diet and exercise, but not in a form that protects muscle, keeps metabolism supported, or can be maintained over time. Years of undereating plus cardio is a totally different animal from eating enough, making protein a priority, and lifting weights consistently.

Do the meds make all of that more manageable? 100%. But those behaviors still shape how far a person gets and whether progress grinds to a halt.

So framing it as meds against lifestyle doesn’t fit for me.

What’s really happening is that the meds finally let lifestyle changes do what they were always meant to do.
GLP medications genuinely address many of the metabolic issues underneath: they lower blood sugar, blood pressure, lipids and insulin resistance, partly through direct drug action and partly because of the weight that gets lost.

When diet and exercise are used as the answer to obesity, even in a highly optimized form, the difficulty lies in the long run. Sustaining that requires deliberate mental effort or restraint, or at least almost always does; turning improved health behaviors into automatic habits is not impossible, but it is hard and most people fail to do it. And the trouble with relying on cognitive effort to solve a long-term problem is that people simply have finite reserves of it, and those reserves eventually run dry. Keeping up that effort is draining both mentally and physically, so eventually old behavior patterns return. To be fair, people with particularly severe obesity are on average probably worse than average at sticking with healthy eating and exercise, which is undoubtedly part of why they became obese. That is not a moral failure; it is just normal human variation, combined with an obesogenic environment, and once obesity develops, exercising becomes harder, and the appetite regulation system begins to progressively malfunction as hormonal and neurotransmitter regulatory systems stop working correctly under the metabolic stress of obesity.

Before GLP drugs existed, long-term weight loss of 5% or more, and rarely 10%, was regarded as a major success in diet-and-exercise treatment for obesity, since even this modest loss substantially lowers long-term health consequences. Everything I have ever seen indicates that any weight-loss intervention short of surgery fails over the long term, with nearly everyone regaining the weight eventually after the intervention stops, and sustaining any intervention long term runs straight into the cognitive effort or cognitive restraint problem.

GLP drugs sidestep the cognitive effort problem entirely, because 1 injection per week is not exactly difficult compared with adhering to a 1600 or 1800 calorie diet long term, and over time they simply keep working as long as you keep taking them. In my view, the evidence from the studies and on this forum demonstrates their effectiveness well, and shows that it is maintained long term. Better diet and exercise matter, but people who take GLP drugs for obesity without making any special lifestyle effort still lose weight. There is also evidence that GLP drugs improve people's food choices, and from personal experience it is far easier to exercise at normal or near-normal weights than when severely obese.

My position is that diet and exercise are a largely ineffective therapy for obesity, judging by long-term results from thousands of studies across decades: not completely useless or pointless, but with very poor long-term success rates. GLP drugs simply work, aside from a few people who get bad side effects or respond poorly to them. For the large majority, though, they enable significant long-term weight loss of 10-30%, with extra health benefits as a bonus.
100% with you. Constantly thinking about food, every single day - what's on your plate, what's coming next, which tactics you'll rely on at holiday gatherings, logging everything, fighting the urge to keep eating once you've reached your limit while your body insists you're still hungry, how to resist the donuts a coworker brought in when you're stressed and hungry, and so on - that's an enormous mental burden, and for the majority of people it simply can't be sustained for a lifetime.

I also know a handful of people who went through the surgery and ended up regaining the weight anyway.
The operation I'd been cleared for was altered by my surgeon. He never put the changes in writing — in effect, my operative report was falsified regarding what he actually did. He only came clean to me once my weight loss halted, after roughly 110 lbs had come off, and after I'd already spent time working with his office to figure out the cause of the stall. When he finally admitted it, I asked when the revision I'd paid for would happen. He told me he didn't believe in revisions, and that I counted as a statistical success since I'd dropped over 100 lbs. I had no way out. Still severely obese. Proving anything was impossible, because his admission came by phone, not on paper. Nothing helped until GLPs. I'll stay on them for the rest of my life.
Have you consulted an attorney? Perhaps an MRI or a similar scan could demonstrate what he did.
 
I'm fully on board, 100%, that diet and exercise alone won't solve the obesity pandemic. Where I differ is on cognitive load being the culprit. My take is that endocrine malfunction is what's driving this. What people call food noise probably comes from too much ghrelin, which happens because of leptin resistance. Test can bring on roid rage, so it stands to reason that other hormones can shape behavior as well.
 
Smiter said:

I'm fully on board, 100%, that diet and exercise alone won't solve the obesity pandemic. Where I differ is on cognitive load being the culprit. My take is that endocrine malfunction is what's driving this. What people call food noise probably comes from too much ghrelin, which happens because of leptin resistance. Test can bring on roid rage, so it stands to reason that other hormones can shape behavior as well.
My view is that the two go hand in hand. Endocrine dysfunction sits at the root, while the cognitive load is what shows up on the surface. Despite already getting plenty of nutrition, our hormones kept signaling starvation. That gap is exactly where GLPs come in, reaching what diet and exercise alone cannot.
 
MsGizmo said:

Vash_ said:

Seriously, why bother? Reta has already been demonstrated to reduce body weight by 30% in people. That alone is absurd. Who actually requires a treatment that works even better?
Me, for instance. My starting point was 334 ... a 30% drop lands me at 234. That's still obese. To get where I need to be, I'd have to shed roughly 50% of what I weighed at the start.

And people don't all respond identically to every receptor ... having choices can only help.
Spot on, you've said it perfectly.
 
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