Experience with 20mg/wk reta?

hypnosisguy

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I am at 12mg/wk reta with 3mg/wk cagri though these numbers may be ~20% low due to overfill. As I approach normal BMI, my loss rate has slowed from .24lb/day to .18lb/day over the past 4 months.

I am considering titrating up again (likely to ~15mg/wk reta, ~4mg/wk cagri), as my loss rate has been sensitive to every titration so far.

I have read on the forum that some people are taking as much as 20mg/wk reta? Can anyone give more information about this? Or about any experience with higher dosages than 12mg/wk? I am less worried about increasing cagri, as that was already tested at 4.5mg/wk in the phase 1 studies.
 
Maybe I’m crazy or just still too naive on the subject, but at what point are GLP-1’s being used as a crutch rather than a tool? I have not personally gotten anywhere near 20mg/week so I’m probably not the best one to answer your question. I’ve pushed myself to 3mg/week and even that feels a little high for me. But I’m on this forum to learn so if I may ask, what do your diet and exercise look like? Are both of those aspects of your life dialed in and you still need the higher dose?

For years lots of people claimed they couldn’t lose weight from a calorie deficit. GLP-1’s have shown that to be true to a degree. They help fix so many things that could be wrong with someone’s body and assist people with weight loss. But at those numbers I have to believe your body is receiving the benefits of a GLP-1 so is there anything else you’re trying to change in your life before titrating beyond FDA-tested clinical trial tested doses of Reta?
 
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Maybe I’m crazy or just still too naive on the subject, but at what point are GLP-1’s being used as a crutch rather than a tool? I have not personally gotten anywhere near 20mg/week so I’m probably not the best one to answer your question. I’ve pushed myself to 3mg/week and even that feels a little high for me. But I’m on this forum to learn so if I may ask, what do your diet and exercise look like? Are both of those aspects of your life dialed in and you still need the higher dose?

For years lots of people claimed they couldn’t lose weight from a calorie deficit. GLP-1’s have shown that to be true to a degree. They help fix so many things that could be wrong with someone’s body and assist people with weight loss. But at those numbers I have to believe your body is receiving the benefits of a GLP-1 so is there anything else you’re trying to change in your life before titrating beyond FDA-tested doses of Reta?
If anything they have proven that false. Eat less, move more, weigh less.
 
Maybe I’m crazy or just still too naive on the subject, but at what point are GLP-1’s being used as a crutch rather than a tool? I have not personally gotten anywhere near 20mg/week so I’m probably not the best one to answer your question. I’ve pushed myself to 3mg/week and even that feels a little high for me. But I’m on this forum to learn so if I may ask, what do your diet and exercise look like? Are both of those aspects of your life dialed in and you still need the higher dose?

For years lots of people claimed they couldn’t lose weight from a calorie deficit. GLP-1’s have shown that to be true to a degree. They help fix so many things that could be wrong with someone’s body and assist people with weight loss. But at those numbers I have to believe your body is receiving the benefits of a GLP-1 so is there anything else you’re trying to change in your life before titrating beyond FDA-tested doses of Reta?
Wasn't aware the FDA has given and guidelines on reta as it's still in clinical trials?
 
Maybe I’m crazy or just still too naive on the subject, but at what point are GLP-1’s being used as a crutch rather than a tool? I have not personally gotten anywhere near 20mg/week so I’m probably not the best one to answer your question. I’ve pushed myself to 3mg/week and even that feels a little high for me. But I’m on this forum to learn so if I may ask, what do your diet and exercise look like? Are both of those aspects of your life dialed in and you still need the higher dose?

For years lots of people claimed they couldn’t lose weight from a calorie deficit. GLP-1’s have shown that to be true to a degree. They help fix so many things that could be wrong with someone’s body and assist people with weight loss. But at those numbers I have to believe your body is receiving the benefits of a GLP-1 so is there anything else you’re trying to change in your life before titrating beyond FDA-tested doses of Reta?
I've lost the same weight before entirely through diet and exercise, and the drugs are far preferable and safer. The first time I lost the weight I also lost my gallbladder. At this weight for me, after a diet and exercise loss, I am in a severely psychologically degraded state, always thinking about food, running many miles a day, and having to eat to a rigorous diet and schedule, with even tiny deviations ready to throw me off the wagon like a drink for an alcoholic. I've been there several times.

To respond to your crazy or naive statement, yes, I think that you are somewhat naive to think that 3mg/wk means the same to you as to everyone else. At 12mg, the phase 2 trials demonstrate that a large number of people are non-responders. Also some people have larger problems with weight than others. What is your current and max BMI? (It's 26 and 49 for me.)

For me, max tirzepatide caused zero weight loss, by the way. I was very much a non-responder, though I had plenty of side effects.

They help fix so many things that could be wrong with someone's body...

I don't believe this is at all true. These drugs have a specific mechanism of action. The other effects are all downstream to the satiety-induced weight-loss. Even proposed effects like specific hepatic-targeted loss are minimal and easier to explain as data issues and downstream of the major weight loss.
 
If anything they have proven that false. Eat less, move more, weigh less.
This is why I said to a degree. Some people experience metabolic rate adaptation resistance. Can you fix that without a GLP-1? Sure, but it’s a lot easier with a GLP-1. There’s also the insulin sensitivity issues that GLP-1’s help with. Can anyone lose weight through calorie deficit? Absolutely. But it’s definitely more difficult for some compared to others.
 
yes, I think that you are somewhat naive to think that 3mg/wk means the same to you as to everyone else
Sorry, didn’t mean to imply that 3mg should work for you. I get people need to titrate up higher, I was simply trying to explain where I’m coming from with my response. First time losing weight I went from 31-23 BMI without taking anything and it took me 2 years. This time I started out at 28 but mostly doing Reta for recomp so I get why my dose is much lower than yours.
I don't believe this is at all true
I think your message proves my point. Sounds like you’ve lost the weight naturally before but it’s easier and better mentally with a GLP-1. Insulin sensitization, reward pathway quieting, and potential leptin interaction aren’t explained by weight loss alone. There’s independent receptor activity evidence. The receptor distribution data suggests more direct central nervous system effects. It’s also widely known that metabolic slowdown happens when losing weight from a calorie deficit. GLP-1’s combat that.

Didn’t mean to come off as aggressive, just trying to say I would be hesitant to go higher on my dose before examining all other aspects of my weight loss plan.

Insulin Sensitivity
 
My bad, *Lilly’s clinical trials
Good Sir, your response seems more like 'griefing' and 'shaming' rather than helping. That said, Hypno . . . I, too, lost a gallbladder and kept getting severe pancreatitis that led to two extended hospital stays due to Keto diets gone amok. No other diets seemed to work after leaving the army . . . combined with a couple of following decades in an office job. Compound tirzepatide and diet have gotten me down to my desired BMI. With the weight loss, exercising became so much easier, despite four autoimmune diseases not in remission. Glp-1s have been life-changing for me. My 400 Ibs brother, on the other hand, has not responded to them. The debate of 'willpower' aside, some souls fare poorly in the genetic lottery. Hypno, I wish you luck in your journey. You might want to also look into some of the excellent posts on microdosing on the forum. This method seems to have helped quite a few folks. Cheers
 
personally i would ask why you would want to titrate up when you are still losing 1.26 lbs a week. that alone would make me incline to believe that the reta is still doing the same amount of work but your bodyweight has dropped enough to directly influence the shift in daily caloric expenditure enough to account for the drop.
if you eat at your goal weights caloric needs the weightloss will slow as you get closer to that level of balance as the calorie deficit gets smaller. unless you just want to try and overshoot it then abruptly increase your calories to balance out?
 
Personally I would not titrate up if I stop loosing weight for 3 weeks. I'm consistently losing about 0.5 to 1lb a week and I am happy with it. Do not really want to lose faster. Been overweight /obese for years, so no rush for me.
Slow and steady.
But hey, you are the researcher and make your own decisions.
 
People need to remember to stop looking at how much you're losing a week in (lbs) on your journey. You need to look at percentages. Sure, while you were huge those numbers were exciting to see but as you get closer to desired BMI it's just not going to be a static expected value.

What percent of body fat in relation to total body weight did you lose in your early stages? What are those numbers currently looking like? What are your macros looking like? How about your training?

This is no stab at you at all but I always hated seeing guys pin Tren and sit on the couch and expect gains. Diet is close to 90% and training is the rest. I don't even give peps a percentage because I view them as a tool to help you achieve the aforementioned goals you've set for yourself.

If you have a detailed log of your day to day progress I'd be more than happy to help you break it down and figure things out.

I personally think 20mg/week of Reta is insane.
 
because I view them as a tool to help you achieve the aforementioned goals you've set for yourself.


I personally think 20mg/week of Reta is insane.
whoa whoa whoa there mister. be carful talking about them as tools. there are some people on this forum with several thousand posts that wont hesitate to tell you how you are wrong and to just up the dose because they are so affordable...i learned that first hand
 
Not exactly the same but there are some similarities. Currently on 16mg tirz plus 5 of reta plus 0.25-0.5 of cagri, only started after weight loss to try to make it a bit easier to tolerate being hungry all the time. Started at 145kg , started ozempic at 75kg 18m ago and swapped to tirz 9 months ago and added the others in , now at 54% down at 66kg.

Unfortunately trying to achieve and maintain losses above 30% or so are out of the scope of the available research. Yet there are a lot of people out there who started with more severe obesity. From what I have read of the research, the combo of reta and cagri is pretty much state of the art in terms of receptor targeting although the combo will not get studied due to being owned by different drug companies. The drug companies are aggressively pursuing research into combination and add on therapies to GLP drugs, so they think the solution for those who respond less well to GLP's or have more severe obesity will lie in combinations.

I find I am limited in terms of doses, even very small increases of 1 mg a week of reta or tirz causes worse skin sensitivity and generally feeling erk, despite not having much in the way of side effects at the doses I am on, other than intermittent mildly annoying skin sensitivity.

So in terms of increasing doses it mainly comes down to adverse effects, if they are not a problem then gradual dose increases are probably reasonable. It is likely a good idea to keep an eye on basic health issues like blood pressure , blood glucose and lipids, for everyone, but especially in the context of severe obesity, and even more so if using experimental higher doses. Even if obesity is dramatically improved, damage could have already been done, and considering cardiovascular risk or assessing if existing damage is present is worth considering. I found out I had very early heart failure and significant coronary artery disease, despite not having symptoms after I lost the weight, even if these cannot be reversed progression can be dramatically slowed by the correct treatment. Anyone with that degree of obesity should be assessed to see if statins and low dose aspirin are needed, and at least an ECG and urine protein checked.

Without being disrespectful to some of the comments above, I think trying to manage severe obesity with BMI's above 40 or 45 is a very different issue to using GLP therapy for BMI's of 30 or 35. The idea of GLP's being a crutch is really the wrong type of thinking. They are a literally lifesaving tool to help manage a very serious illness, that untreated has horrible and almost inevitable long term health consequences. That degree of obesity increases cardiovascular risk by around 40 times, worse than smoking or diabetes. In that context I think using combination therapies or doses above standard ones is likely to be a reasonable risk. Yes it could have serious long term side effects, but not using them almost certainly has worse and much more likely severe long term consequences.

Obviously staying on them long term is critical to maintain the weight loss, and in that context they are justified solely for cardiovascular risk reduction . You might be able to reduce doses a bit once you get to a weight you are happy with, but even if you cannot quite get there, the weight loss already achieved is enough to reduce health risks towards normal levels, after that fitness probably matters more than exact weight.
 
Not exactly the same but there are some similarities. Currently on 16mg tirz plus 5 of reta plus 0.25-0.5 of cagri, only started after weight loss to try to make it a bit easier to tolerate being hungry all the time. Started at 145kg , started ozempic at 75kg 18m ago and swapped to tirz 9 months ago and added the others in , now at 54% down at 66kg.

Unfortunately trying to achieve and maintain losses above 30% or so are out of the scope of the available research. Yet there are a lot of people out there who started with more severe obesity. From what I have read of the research, the combo of reta and cagri is pretty much state of the art in terms of receptor targeting although the combo will not get studied due to being owned by different drug companies. The drug companies are aggressively pursuing research into combination and add on therapies to GLP drugs, so they think the solution for those who respond less well to GLP's or have more severe obesity will lie in combinations.

I find I am limited in terms of doses, even very small increases of 1 mg a week of reta or tirz causes worse skin sensitivity and generally feeling erk, despite not having much in the way of side effects at the doses I am on, other than intermittent mildly annoying skin sensitivity.

So in terms of increasing doses it mainly comes down to adverse effects, if they are not a problem then gradual dose increases are probably reasonable. It is likely a good idea to keep an eye on basic health issues like blood pressure , blood glucose and lipids, for everyone, but especially in the context of severe obesity, and even more so if using experimental higher doses. Even if obesity is dramatically improved, damage could have already been done, and considering cardiovascular risk or assessing if existing damage is present is worth considering. I found out I had very early heart failure and significant coronary artery disease, despite not having symptoms after I lost the weight, even if these cannot be reversed progression can be dramatically slowed by the correct treatment. Anyone with that degree of obesity should be assessed to see if statins and low dose aspirin are needed, and at least an ECG and urine protein checked.

Without being disrespectful to some of the comments above, I think trying to manage severe obesity with BMI's above 40 or 45 is a very different issue to using GLP therapy for BMI's of 30 or 35. The idea of GLP's being a crutch is really the wrong type of thinking. They are a literally lifesaving tool to help manage a very serious illness, that untreated has horrible and almost inevitable long term health consequences. That degree of obesity increases cardiovascular risk by around 40 times, worse than smoking or diabetes. In that context I think using combination therapies or doses above standard ones is likely to be a reasonable risk. Yes it could have serious long term side effects, but not using them almost certainly has worse and much more likely severe long term consequences.

Obviously staying on them long term is critical to maintain the weight loss, and in that context they are justified solely for cardiovascular risk reduction . You might be able to reduce doses a bit once you get to a weight you are happy with, but even if you cannot quite get there, the weight loss already achieved is enough to reduce health risks towards normal levels, after that fitness probably matters more than exact weight.
Well said and well written.

I think it's worth mentioning that assessing what other metabolic dysfunction people having going on is crucial. You're going to need a great doctor or at the very least find one who will send you for a litany of blood work, especially some certain markers at your request because average GP's have no clue about these things.

Thankfully we have many more tools in our arsenal!

I'm working with a fella right now who was extremely obese, triple bypass, HF... you name it. He's down from 400lbs to 350 in 3 months now. I want him down to 220 in the next 64 weeks. His fasted glucose has come down significantly and his insulin sensitivity has risen dramatically. I'm not telling him what to take or what to do in just nudging him in the right directions and have provided him with a meal plan and exercise routine free of charge because I care about the guy.

I care about everyone, a little too much at times.

My Wife once said to me, "You can't save all the whales (name)!"

No pun intended on her part but kind of funny 🤣 🤣
 
One thing I would ponder when scaling up dosages of GLPs beyond the studied doses is what risks could come with very high doses (aside from more severe forms of the usual/obvious side effects). Since reta does act as a glucagon agonist, it would be reasonable to ask if that component of it might lead to anything unexpected at higher dosing. Although GLPs in general raise insulin to a certain degree, that increase is limited by what your beta cells can actually produce (no matter how hard you push the GLP agonist lever). In the case of reta, it's not causing your alpha cells to produce more glucagon, but simulating the effect of glucagon directly (the "fake" glucagon is built into the reta molecule itself). This means as you increase the dose of reta, you keep increasing the effective glucagon level in your blood, without your body able to dictate an upper limit.

I will admit that there is a part of me that wonders just how safe continuous 24/7 glucagon agonism is in general. Guess we'll all find out the answer of that together in 5 to 10 years! LOL
But my point is that glucagon is a bit of a wildcard and I would probably wonder if adding some tirzepatide might be a less bad compromise VS pushing reta outside of the study range. I mean it's probably okay, but none of us really know.

There's also the option of pulling other levers, such as a GHRH analog. Don't know if there's a ton of people stacking reta + cagri + tesa, though and I'm certainly not recommending that (or anything else) for that matter.
 
I actually tried an experiment when I was at 12mg. Week 1 - 13mg; week 2 - 14mg; week 3 - 15mg; then back down to 12mg. Honestly, I couldn't tell the difference. No increases in side effects, weight loss or anything. Just the same steady weight loss I had before.
 
whoa whoa whoa there mister. be carful talking about them as tools. there are some people on this forum with several thousand posts that wont hesitate to tell you how you are wrong and to just up the dose because they are so affordable...i learned that first hand
lol learning this too now. I guess I’ve spent too much time on Meso? Didn’t think asking a question about diet and exercise would be so offensive. Lift weights, do LISS cardio, track your protein/macros and most of the time you’ll lose weight. Throw in Reta and you’ll for sure lose the weight. Relying on a drug as the primary contributor to losing weight doesn’t make sense to me. Can you get more sleep? Can you increase your steps by 3k a day? Can you adjust your diet a little bit? I feel like these are the questions to ask before going past the max tested dose of a drug, especially when it’s still working.
 
Relying on a drug as the primary contributor to losing weight doesn’t make sense to me.

Probably because you don't have a GLP deficiency, or much of one anyway. In which case GLPs are more like a tool, because you never needed them in the first place.

Related threads:

 
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lol learning this too now. I guess I’ve spent too much time on Meso? Didn’t think asking a question about diet and exercise would be so offensive. Lift weights, do LISS cardio, track your protein/macros and most of the time you’ll lose weight. Throw in Reta and you’ll for sure lose the weight. Relying on a drug as the primary contributor to losing weight doesn’t make sense to me. Can you get more sleep? Can you increase your steps by 3k a day? Can you adjust your diet a little bit? I feel like these are the questions to ask before going past the max tested dose of a drug, especially when it’s still working.
If you dare mention to anyone on reddit to move a little bit more you're on the verge of getting banned. 🤣

Think it's remnants of the body positivity movement that moved over to just jabbing themselves and not making any lifestyle changes at all.
 
Probably because you don't have a GLP deficiency, or much of one anyway. In which case GLPs are more like a tool, because you never needed them in the first place.
I'm all for skipping "moralizing" arguments about weight loss, but for the most part "GLP deficiency" is a fictitious concept. Humans didn't suddenly evolve a GLP deficiency over two generations.

Now it is documented that statins reduce GLP production, so if you're taking one, that's legitimately a GLP deficiency (and likely why statin use is associated with an increased risk of diabetes). I'm sure other drugs do the same and modern processed food is surely contributing as well (not to mention dozens of other inputs that impact us in subtle ways).

Let's just agree that some people are going to rely primarily on GLPs as the weight control measure, while others are going to utilize them more as a boost on top of lifestyle improvements. Both approaches beat doing nothing. I think it's our own insecurities that cause us to take offense when others note that lifestyle still plays into overall results.
 
One theory: "Glucagon-like peptide-1 (GLP-1) deficiency occurs in obesity-related pathologies due to defects in the intestinal lumen. And expanding the L-cell population has emerged as a promising avenue to elevate GLP-1 secretion to tackle metabolic disorders."

Regardless of "GLP deficiency" vs. "functional impairment," L-Cells look interesting (as does DPP-4):

The functional capacity of L cells and overall intestinal GLP-1 production depend critically on L cell survival. Therapeutic strategies aimed at enhancing L cell viability and preserving their population could represent a novel approach for addressing obesity-related disorders [27].

Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control
Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion.

What Is an L-Cell and How Do We Study the Secretory Mechanisms of the L-Cell?
1774978705583.png
L-cells in non-human primate colon (Cynomolgus macaque). L-cells were identified based on proglucagon immunoreactivity (green). In upper panel two L-cells are shown. Lower panels shows a close-up of the L-cell in the upper panel (indicated by arrow). At the highest magnification, the individual GLP-1 granules are visible. Cell outlines are labelled by e-cadherin (red) and nuclei are stained with DAPI (grey).
 
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Probably because you don't have a GLP deficiency, or much of one anyway. In which case GLPs are more like a tool, because you never needed them in the first place.
Is it fair to assume that getting down to a healthier BMI level will fix those deficiencies? Or do they stay with someone forever? In this case the user said they’re at a 26 BMI currently. I’m not saying I don’t understand higher doses in higher BMI individuals, but once you start getting to your goal weight shouldn’t you be wanting to transition towards titrating down and forming habitual lifestyle changes?
 
Is it fair to assume that getting down to a healthier BMI level will fix those deficiencies?
I'm sure for some people. Not looking good though in general, based on the SURMOUNT results, where people gained a good amount of weight after stopping tirz (and kept gaining weight):


OTOH:
That's the exact result I'd expect, if I'm being honest.

Had the "lifestyle" intervention been sufficient to converge at a BMI of 25 (or whatever target one chose) then there would have been no need for the drug in the first place. The problem is that the primary lifestyle driver chosen was simple calorie-restriction. That's obviously going to break down when you take away the drug that enables easy calorie-restriction.

In any case, a number of people here (including myself) would prefer to stay on GLPs for life for the health benefits, less food noise, etc:

I like that graph a lot , very clear signal about what happens when it is stopped, and a strong argument for staying on glp-1 agonists for maintenance. But even for those who stopped there are still significant benefits in terms of weight and long term risks. Before these medications were available research would talk about the metabolic and risk benefits of 5-10% weight loss, and that those benefits were still significant.

I am surrounded by calories all day long, so I really appreciate not being tempted on GLPs. And the food environment in the average American kitchen is horrible, unless you decide to live alone or have a family that is on board.
 
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One theory: "Glucagon-like peptide-1 (GLP-1) deficiency occurs in obesity-related pathologies due to defects in the intestinal lumen. And expanding the L-cell population has emerged as a promising avenue to elevate GLP-1 secretion to tackle metabolic disorders."

Regardless of "GLP deficiency" vs. "functional impairment," L-Cells look interesting (as does DPP-4):



Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control


What Is an L-Cell and How Do We Study the Secretory Mechanisms of the L-Cell?
My personal theory is that since GLPs have proven so effective it causes people to hyperfixate on the role of just that particular hormone in hunger signaling. Then you have companies marketing "naturally raise your GLP" nonsense to try to cash in on the hype too. Just like how in 5 years (after reta is out for a bit), I'm sure other researchers will frame obesity as "inadequate glucagon signaling."

The problem with that theory is that for most it's not a hunger problem (although that's how we experience it), but more of a metabolic issue where obesity is just one of the ways in which a deranged metabolism can manifest itself. Suppressing hunger (via off the charts GLP signaling) helps achieve weight loss for sure. If it was an issue of GLP being 10% to 15% too low then I might buy the GLP deficiency story, but we're not bumping it up 10% to 15% with these drugs. We're bumping it up many orders of magnitude higher to levels that could never be achieved in nature. It's a clever hack to resolve a problem somewhere else in the system.
 
To bring back the steroids metaphor, I see it as going from clinically low testosterone to supraphysiological testosterone:

Gemini said:
CategoryGLP-1 Status / ActivityKey Study / Evidence
Lean Individual100% (Baseline)Postprandial (after-meal) secretion is robust; baseline for healthy metabolic signaling.
Obese Individual~20% to 25% ReductionSignificant reduction in post-meal GLP-1 and GLP-2 compared to lean controls.
5 mg TirzepatideSupraphysiological Saturation5 mg dose provides continuous receptor activation, leading to ~12-15% weight loss (SURPASS-1).
PharmacologyGIP/GLP-1 SynergyTirzepatide is a "biased" dual-agonist; GIP component enhances the overall metabolic "oomph."
MechanismsHalf-life ExtensionNative GLP-1 lasts ~2 minutes; Tirzepatide lasts ~5 days, creating constant "shouting" at the brain.

But unlike the AAS bros on controlled substances, we don't need to worry about stopping GLPs for health reasons. The opposite is true.
 
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