Hi I’ve been using reta for about 3 months now, I used it before last year where I only needed 2.5mg to feel the effects and appetite suppression. However when I started again a couple months ago I started on 5mg for a couple weeks then moved to 10mg for a month and still felt good appetite suppression, then I decided to mix in 5mg of tirz when the effects were going down which boosted the suppression again. When I finished with the tirz after 2 weeks I started 20mg reta and can’t feel anything at all in terms of suppression. Can someone explain why this is, do I need a break and for how long because I thought glp receptors can’t build tolerance.
Retatrutide problem
- Thread starter A1stg
- Start date
Calm Logic
GLP-1 Specialist
20 mg, not 2 mg, right?
What about weight loss or gain? Or is the scale just the same every week?
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At first I was experiencing a lot of weight loss like very quickly but then as my suppression for appetite decreased and I upped the dosage it became stagnant. Lost 20kg. And yeah 20mg
zpped
Moderator
That is an absurd amount of drug abuse you are doing there.
zanny-kanny
GLP-1 Apprentice
Hi and welcome!
I agree that we need a little more info in order to help you figure out your problem. Namely: how many months were you on Reta the first time, what mg were you on when you ended and how much weight did you lose? Why did you stop the Reta, and how long were you off? Why did you start at 5 mg this time instead of titrating slowly up? How did you go from 5 to 10 mg in a month? And were you losing weight on Reta only?
I don't agree with stacking 2 GLP1s because they do the same thing and work on the same receptors - I'm thinking receptor overload. But you can also develop antibodies to Reta and I'm sure Tirz and the other GLP1s, as well as other peptides (tesamorelin for one).
Retatrutide antibodies can neutralize its effects. When peptides like retatrutide are injected, the immune system may produce antibodies that target them, leading to a condition known as Anti-Drug Antibody (ADA) formation, which can diminish their effectiveness. Additionally, the use of specific antibodies, such as a GCGR antibody antagonist, has been shown to minimize the weight loss effects associated with retatrutide, indicating that antibodies can play a significant role in how retatrutide functions in the body.
I agree that we need a little more info in order to help you figure out your problem. Namely: how many months were you on Reta the first time, what mg were you on when you ended and how much weight did you lose? Why did you stop the Reta, and how long were you off? Why did you start at 5 mg this time instead of titrating slowly up? How did you go from 5 to 10 mg in a month? And were you losing weight on Reta only?
I don't agree with stacking 2 GLP1s because they do the same thing and work on the same receptors - I'm thinking receptor overload. But you can also develop antibodies to Reta and I'm sure Tirz and the other GLP1s, as well as other peptides (tesamorelin for one).
Retatrutide antibodies can neutralize its effects. When peptides like retatrutide are injected, the immune system may produce antibodies that target them, leading to a condition known as Anti-Drug Antibody (ADA) formation, which can diminish their effectiveness. Additionally, the use of specific antibodies, such as a GCGR antibody antagonist, has been shown to minimize the weight loss effects associated with retatrutide, indicating that antibodies can play a significant role in how retatrutide functions in the body.
Calm Logic
GLP-1 Specialist
Sounds like a typical stall, except for the 20mg of reta. The more weight you have already lost, the harder/slower it can be. And 20 kg (44 pounds) is significant.
For stalls, I try to focus on body composition, rather than the unmoving number on the scale.
How is your energy level? Are you as active as you were before?
For stalls, I try to focus on body composition, rather than the unmoving number on the scale.
How is your energy level? Are you as active as you were before?
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zanny-kanny
GLP-1 Apprentice
Possibly but she has definitely engaged in some peptide abuse. Who knows what kind of damage she has done to her receptors by upping her dosage to those ridiculous amounts so quickly? Jeez, I never went above 10 mg and I've now lost 113 lbs.
Calm Logic
GLP-1 Specialist
How much weight that is left to lose can also be a factor.
But receptors are not damaged. There would just be greater tolerance to the higher dosing. Like with the heart stimulant clenbuterol, you can't fry your beta-2 receptors, even at higher doses. But higher doses eventually become less effective, as the receptors can be activated only so much at one time.
But receptors are not damaged. There would just be greater tolerance to the higher dosing. Like with the heart stimulant clenbuterol, you can't fry your beta-2 receptors, even at higher doses. But higher doses eventually become less effective, as the receptors can be activated only so much at one time.
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zanny-kanny
GLP-1 Apprentice
Still damage. There is also the antibody issue. If it develops it can neutralize (make ineffective) the peptide for future use.
I understand your point, but I didn't jump quickly from 5 to 10 to 20 in 2 months. I would suggest that this person needs to take it more slowly and give some more thought (and research) about how to wisely use these peptides to achieve her goals.
I understand your point, but I didn't jump quickly from 5 to 10 to 20 in 2 months. I would suggest that this person needs to take it more slowly and give some more thought (and research) about how to wisely use these peptides to achieve her goals.
Calm Logic
GLP-1 Specialist
For GLPs, the antibody issue would not be dose-dependent and would have more to do with slight increases in injection-site reactions, for the two percent or so of the patients who develop the antibodies.
zpped
Moderator
The tirz antibodies were determined to be non neutralizing. They suck. But they don't cause it to stop working.
The real biggest concern is gastroparesis. These drugs aren't without risk.
The real biggest concern is gastroparesis. These drugs aren't without risk.
Calm Logic
GLP-1 Specialist
FlowerFairy
GLP-1 Enthusiast
You don’t need to be taking that much Reta. That’s not anything but drug abuse. You need to either back down and add cagri for appetite suppression or switch to a different GLP. That dose is insane.
Calm Logic
GLP-1 Specialist
Stalls can be emotionally taxing. Wondering if this is as good as it gets, etc. So I wonder what triggered the desperation/experimentation. Body image issues? Or feeling too much uncertainty? And how much weight are you trying to lose still?
Also, are you on any AAS, HGH, prescriptions, recreational drugs, or any peptides that may increase appetite?
Also, are you on any AAS, HGH, prescriptions, recreational drugs, or any peptides that may increase appetite?
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DR.D.
GLP-1 Novice
These things need to be cycled! You can stack and switch, and mix and match until it works again, but at some point your liver is just too educated and you have to take a break. You make enzymes to degrade these things, and they are likely very upregulated at the moment, necessitating an ever increasing dose. At some point, it stops really working and you're just left with side effects.
Its generally necessary to take AT LEAST at 2-3wk holiday every 6 months (or sooner) or these peptides will often completely play out. Once you've taken a good break, 6-8wks is even better, then you can rechallenge and the lower doses will likely be effective once again.
People experiencing side effects are often the ones who get greedy and max out the dose, for way too long.
I'd suggest a break from all GLPs. There are plenty of other compounds you can consider to pick up the slack in the off time, that work by other mechanisms that won't prevent a good recovery. Tesofensine, or other classic phenethylamine based appetite suppressants for example, and don't fail to consider all the non-stims options that are available too.
zpped
Moderator
I'm calling bullshit. Point to one piece of evidence from any human trial of glp1 that even suggests this might true.
Also bullshit. Side effects are dose dependent but they get better from staying at the same dose not worse.
PackmanJohnny
GLP-1 Apprentice
TWENTY?!?!?!
FUCKING TWENTY?!?!
TWENTY.
nah, at that point you gotta flush anything you got left and pick a different hobby. 20 is actually insane. over a stall? Dawg.
FUCKING TWENTY?!?!
TWENTY.
nah, at that point you gotta flush anything you got left and pick a different hobby. 20 is actually insane. over a stall? Dawg.
zpped
Moderator
My bet is they didn't test their kit and its not reta. Or they are terribly bad at recon math.
FlowerFairy
GLP-1 Enthusiast
Name one diabetic told to “take a break” from tirzepatide. These drugs were created for diabetics and there is no requirement to “reset their receptors”. It’s bro science.
DR.D.
GLP-1 Novice
Are you kidding?! Have you ever used a GLP long-term?
And what does a diabetic have to do with it? lol
It's just a matter of common experience that you develop drug tolerance, especially with synthetics. Name one person you know that started on 2.5mg and is still getting results without have to go up to 5+mg after 6 months. I don't know anybody who's done that. You have to up the dose, stack it with something else, or take a holiday.
It's a matter of subjective experience, bro, lol. You're in dangerous denial if you need a study to explain away what your experiencing in real life.
DR.D.
GLP-1 Novice
Bullshit? On what??
Do you think your body fails to equilibrate to new drugs you start using? Tolerance is a matter of common experience, and a WELL established biological phenomena. It generally takes 2-3wks for your response to begin, and it's usually driven mostly by inducible enzymes. It really cant be avoided, not without some tricky maneuvers, like use of other drugs to compensate for it.
Side effects don't always go away either. Sometime sensitization occurs, and they get worse at the same dose, or even lower, so not sure what your point is with all that.
And yes, side effects generally are dose dependent, I never said otherwise, so not sure what that 'bullshit' call was about.
You just seem a little belligerent, my friend. Sorry, didn't mean to trigger anyone.
PackmanJohnny
GLP-1 Apprentice
It is harder for some than others. I got to save a buddy of mine's life the other day - he told me he was plannig a Test cycle of 400MG/Day... He asked me why it was so expensive.
peptidepower77
GLP-1 Apprentice
Some people just get caught up with the hype and the bro science. I have a friend who is rather intelligent and was happily taking TRT under doctor supervision at 120mg/week with normal levels. He got the bright, bro-filled idea to blast 300-400mg one week thinking it would be a fun experiment. Not long after he felt ill and his hematocrit was dangerously high and the ER doctors were freaked out. He has one of the gene defects where he already has a hard time clearing iron, so I think it compounded with the high T. He ended up quitting entirely at that point because he freaked himself out so bad.
PackmanJohnny
GLP-1 Apprentice
Holy hell...
It almost seems like the TRT doctor should have caught an indicator for that in his bloods, but who knows, Im not a doctor. 300-400 should be relatively safe for most. I cruise at 250mg/week and have for several years now. blasts usually go to 500-750, but i cut those off at 8 weeks.
peptidepower77
GLP-1 Apprentice
Yah he has a subtle form of hemocromatosis, which is iron overload, so his hematocrit was already on the edge. When he blasted it pushed him way over, and his blood became super thick, dangerously so. This all happened in the course of a week, so without that ER visit he wouldn't have seen it.
zpped
Moderator
Yes. Personally for over a year and I talk with people who have been on them much longer.
The original purpose of these drugs is for glucose control, so a fair bit of relevance. But the analogy is whats important. Take blood pressure medication, once a proper dose is found that brings your pressure down a good level, you stay on that dose for the rest of your life.
Some drugs build tolerance, most don't. People that lost a certain amount of weight with 2.5mg will keep that weight off as long as they are on the drug. That is equilibrium for that specific dose for that person not tolerance, that would be gaining weight.
Taking time off/cycling these drugs is counter productive, dumb, and not backed up by the tons of studies on these specific drugs.
You made some very strong claims and I asked you to back it up with some evidence. You chose to double down and claim "it's common sense". You could have tried to bring up the one study that showed glp-1 tolerance but it's only in mice and it's never been seen in humans in all the other studies.
Calm Logic
GLP-1 Specialist
You cruise GLPs. You cycle McDonald's and Domino's.
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zanny-kanny
GLP-1 Apprentice
That's tirz. We are discussing Reta in this situation. The Clinical study II discovered that 50% of the participants developed antibodies to it during the length of the 48 week study. That's pretty significant. They also cannot determine if it resulted in neutralization or desensitization because that wasn't the purpose of the study. Only time will tell if these folks will be able to use this again in the future and achieve any real kind of weight loss.
Receptor Desensitization and Neutralization are real and need to be better understood and studied with these new weight loss drugs. I experienced it 30 years ago when I had to go off a drug for surgery for a month. I had been taking the drug for a little over a year. When I resumed the drug it no longer worked. It was being used for pain relief (horrible pain) and I had to resort to a year of steroid shots before the pain subsided.
In a recent article I read about a fellow who used CJC-295/Ipa as directed by a physician - cycled with weeks on followed by a certain number of weeks off. It worked beautifully until he attempted to resume the next cycle, when it failed miserably and he actually gained weight and had to abandon his treatment.
Because of my personal experience I refuse to 'cycle off' peptides. I reduced Reta but never stopped it and it is still working for me going on 13 months. I've never done the 5 days on/2 off recommended protocol for tesamorelin (not sure where that came from, studies I've read have all been daily for 26 weeks) and it is still working great (on week 11)
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That’s the only reason I rlly went up to 20 I thought it was bunk, I got it from SSA which I thought were legit. I’ve ordered a test from Janoshik but am still gonna take a long break and use cagrillintide. 50mg vial 2.5ml reconstruction 1ml per injection my maths isn’t bad
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