Anyone on GLP-1's for multiple years?

[ChemBB]

I was RX'ed Mounjaro 2 years ago, and have been using various GLP-1's ever since.

tl;dr, at least in terms of appetite, they are doing fuckall for me now
I'm up to 10mg Reta + 3mg Sema and still so hungry, not losing weight anymore.

At this point I'm considering just pinning a vial of Reta E3D, may as well be sugar water...

Anyone else dealt with/overcome this?

 

[Deadpool99]

Sounds interesting, but damn is it expensive compared to just buying more Sema/Tirz =/

A kit from a more expensive domestic supplier like Amo/bff costs like $90 for a 5mg kit. Less than a week for delivery and zelle as payment.

Theoretically 50mg at my current 1.5mg dose should last me 33 weeks. I feel like 1.5mg is very aggressive, you might not reach 1.5mg as quick as me. I’m the guy who would up his reta from 9mg to 12mg in the same week.

Edit: Turns out the domestic price is the same as the HYB china warehouse price-list.

 

[Ghoul]

I was RX'ed Mounjaro 2 years ago, and have been using various GLP-1's ever since.

tl;dr, at least in terms of appetite, they are doing fuckall for me now
I'm up to 10mg Reta + 3mg Sema and still so hungry, not losing weight anymore.

At this point I'm considering just pinning a vial of Reta E3D, may as well be sugar water...

Anyone else dealt with/overcome this?

A small percentage of people are genetically "GLP non-responders". This can even be accurately predicted with a commercially available genetic test.

Subsequent research by Novo Nordisk seems to indicate no one is truly a non-responder, but a "low / slow responder". Likely some kind of receptor issue.

Anyway, what Novo did for those who lost no weight at 2.4mg Sema, was boost the dose to 4.8mg, then 7.2mg.

It's been demonstrated safe in large scale trials, but more importantly, by 7.2mg 100% of previous non-responders lost significant weight.

They will be releasing these increased doses soon.

Sema is cheap. You can try simply upping the Sema until you get the effect you want, all the way to 7.2mg knowing it's not an issue (not all in one big titration of course.).

 

[keengkong]

A kit from a more expensive domestic supplier like Amo/bff costs like $90 for a 5mg kit. Less than a week for delivery and zelle as payment.

Theoretically 50mg at my current 1.5mg dose should last me 33 weeks. I feel like 1.5mg is very aggressive, you might not reach 1.5mg as quick as me. I’m the guy who would up his reta from 9mg to 12mg in the same week.

Edit: Turns out the domestic price is the same as the HYB china warehouse price-list.

I don't count Amo/BFFlink as domestic supplier. I know they have a domestic warehouse but I have never heard it claimed that the company is based domestically.

 

[sionnach]

I was RX'ed Mounjaro 2 years ago, and have been using various GLP-1's ever since.

tl;dr, at least in terms of appetite, they are doing fuckall for me now
I'm up to 10mg Reta + 3mg Sema and still so hungry, not losing weight anymore.

At this point I'm considering just pinning a vial of Reta E3D, may as well be sugar water...

Anyone else dealt with/overcome this?

Reta is signaling to your brain "Hey, we're burning fat and making blood sugar out of protein down here." which the normal non-reta human brain usually interprets as "Oh shit, we need to eat something." (aka hunger) but you should reprogram your brain to translate it as "Oh good, my vials of sketchy chinese powder weren't a waste of money!"

It took me a while too. I even tried cagri and tirz with the reta, but eventually I settled on just reta and discipline.

 

[Deadpool99]

I don't count Amo/BFFlink as domestic supplier. I know they have a domestic warehouse but I have never heard it claimed that the company is based domestically.

Oh yes, you are correct. Sorry for the misunderstanding. They are china based with a domestic warehouse and operate domestically but aren’t based in the US.

I just name them as my domestic source as I don’t rly order from US based companies for my peptides. Never worth the price imo.

 

[zzzz]

Try Cagri, for someone who reached 15mg reta and eats clean volume foods while stacking a shit ton of fiber into my drinks/ninja creamis (glucomannan/physiullum husk/Fibersol-2) and still get’s hungry. Cagri does a good job.

Those ninja creami pints are as satiating as a family gathering dinner, ppl who try it can’t finish it in an empty stomach. For me it’s an appetizer.

If you’re like me and get used to drugs fairly quickly or tolerate them well. Cagri hits a different hormone receptor, so it’ll def help u, atleast short term. It’s helping me push past the last few weeks of my cut.

I didn't feel anything at all from 1.25mg cagri. Like just no change, as if I was given placebo. Based on Reddit posts of people saying they had their appetite completely wiped from 0.25mg I just assumed I was a non responder and never bothered restocking the vial after finishing.

Do you think I just need a higher dose and it's worth trying again?

 

[Deadpool99]

Reta is signaling to your brain "Hey, we're burning fat and making blood sugar out of protein down here." which the normal non-reta human brain usually interprets as "Oh shit, we need to eat something." (aka hunger) but you should reprogram your brain to translate it as "Oh good, my vials of sketchy chinese powder weren't a waste of money!"

It took me a while too. I even tried cagri and tirz with the reta, but eventually I settled on just reta and discipline.

I don’t rly associate hunger on GLP1’s with not being disciplined. I assume some people are like me and just never feel full enough no matter the caloric intake, cleanness and volume of food.

I have very good discipline but the pure life changing experience of having to put the fork down cuz I’m actually full and can’t each more, is just so amazing.

365 days a year, everyday I have to plan my dinner and meal meticulously, so that I eat the most volume so I maximize the feeling of fullness. I never opt to go to fine dining and cafes because I could never be remotely full like the rest if the population. So I have to opt for the most volume for the least calories even on a bulk.

The appetite suppression makes life way easier, and simplifies my life choices without hassle and overthinking.

 

[Liter O' Test]

long term i dont even care about the appetite. the blood glucose control is key. being insanely insulin sensitive and keeping blood sugar low, that keeps the fat off.

 

[Deadpool99]

I didn't feel anything at all from 1.25mg cagri. Like just no change, as if I was given placebo. Based on Reddit posts of people saying they had their appetite completely wiped from 0.25mg I just assumed I was a non responder and never bothered restocking the vial after finishing.

Do you think I just need a higher dose and it's worth trying again?

First I’d try and evaluate you’re source. How likely was it legit?

 

[Deadpool99]

long term i dont even care about the appetite. the blood glucose control is key. being insanely insulin sensitive and keeping blood sugar low, that keeps the fat off.

That’s the only reason I keep reta tbh, I could probably just roll with cagri high dose but reta’s BG is why it’s a must have for me.

I trust it’s working as I never had BG issues when I started but then I used HGH and I was already on reta. So I assume it’s helping my BG, at-least every piece of literature suggests that. 10iu blast without metformin/SLGT2 at the time and my BG was perfect. Atleast in my situation.

 

[Deadpool99]

Oh yes, you are correct. Sorry for the misunderstanding. They are china based with a domestic warehouse and operate domestically but aren’t based in the US.

I just name them as my domestic source as I don’t rly order from US based companies for my peptides. Never worth the price imo.

Also a moment of silence for the gift of the Chinese peptide vendors. I used to buy a vial of 12mg reta for $140 (I considered cheap compared to the other US based sources as well at the time).

I was trying to get away either 2mg for months like a meth addict trying to savor what’s left of his supply.

 

[keengkong]

I was RX'ed Mounjaro 2 years ago, and have been using various GLP-1's ever since.

tl;dr, at least in terms of appetite, they are doing fuckall for me now
I'm up to 10mg Reta + 3mg Sema and still so hungry, not losing weight anymore.

At this point I'm considering just pinning a vial of Reta E3D, may as well be sugar water...

Anyone else dealt with/overcome this?

I've been on tirz for 14 months. It's still working for me. In general, tirz won't suddently stop working. See Jastreboff, et al. (2025). Tirzepatide for Obesity Treatment and Diabetes Prevention. New England J. Med., 392(10), 958 [describing weight loss lasting over three years].

 

[sionnach]

I don’t rly associate hunger on GLP1’s with not being disciplined.

That's not really what I meant anyway.

The appetite suppression makes life way easier, and simplifies my life choices without hassle and overthinking.

True. But reta's not very active at GLP-1, and its activity at the other two sites can actually make you feel hungrier, even outpacing activity of additional GLP-1s. I found it effective to think of that hunger as success when cutting, or just give in to it (responsibly) when reta bulking. We're all a little body dysmorphic already at Meso, why not use some extra psych tricks to take advantage of our broken brains.

 

[Deadpool99]

That's not really what I meant anyway.


True. But reta's not very active at GLP-1, and its activity at the other two sites can actually make you feel hungrier, even outpacing activity of additional GLP-1s. I found it effective to think of that hunger as success when cutting, or just give in to it (responsibly) when reta bulking. We're all a little body dysmorphic already at Meso, why not use some extra psych tricks to take advantage of our broken brains.

Oh ok I understand your perspective now. Eventually even on Reta as I said I do get hungry, and yeah eventually you have to accept it the hunger and embrace it, I didn’t mind it cuz ik it mean I’m doing smth right. But if you can suppress it, I swear if it feel like a cheat code.

I literally ate like 500g homemade fries and a 2 cans of tuna. And I can’t finish my bottle of pepsi zero (this has never happened before and I’m so happy, I am also a pepsi zero addict, I swear my monthly budgeting is like $450 on pepsi zero)

 

[Banana Joe]

... reta's not very active at GLP-1, and its activity at the other two sites can actually make you feel hungrier, even outpacing activity of additional GLP-1s.

I wish that would be the case for me, but it surely isn't.

I wonder how far we are away from a Reta-like drug, without appetite suppression and slowed down gastric emptying, but all the other benefits.
If that is even somehow remotely possible.

 

[Deadpool99]

I wish that would be the case for me, but it surely isn't.

I wonder how far we are away from a Reta-like drug, without appetite suppression and slowed down gastric emptying, but all the other benefits.
If that is even somehow remotely possible.

I guess if they work on improving some current drugs like the one I’m using. I have a combo of Metformin/Jardiance(Empagliflozin) and gonna experiment with Acarbose on my bulk when I’m eating a big ass 200g+ meal.

 

[sionnach]

I wish that would be the case for me, but it surely isn't.

Ahh just roll with it and get fuckin leeeeeeean.

that is even somehow remotely possible.

Sure it is. The real question is, has Lilly found a way to market it at $1000/mo?

 

[Deadpool99]

I wish that would be the case for me, but it surely isn't.

I wonder how far we are away from a Reta-like drug, without appetite suppression and slowed down gastric emptying, but all the other benefits.
If that is even somehow remotely possible.

Btw I was searching a compound that sounds like this and seems like a bodybuilder’s dream. Curious if have you heard about this one @Ghoul.

It’s called, Bimagrumab.
Bimagrumab is basically a “monoclonal antibody” that blocks smth called activin type II receptors (ActRIIA/B), which normally binds to proteins like myostatin and activin which suppress muscle growth.

So by inhibiting those pathways, bimagrumab removes the body’s natural “muscle-growth brakes,” so it leads to an increased lean mass, reduced fat mass (especially visceral fat) and improved insulin sensitivity.

It works entirely peripherally, without acting on appetite centers or slowing digestion, which makes it fundamentally different from GLP-1–based drug.

Clinical studies in people with obesity and type 2 diabetes have shown that bimagrumab can simultaneously build muscle and reduce fat, lowering A1C and fasting glucose without changes in diet or calorie intake.

It’s been well tolerated in trials lasting up to a year, with only mild side effects such as rash or diarrhea, though its long-term safety remains unproven.

In a nutshell, bimagrumab aims to improves body composition and metabolic health without the appetite suppression or GI issues typical of GLP-1 drugs.

 

[RockyP]

In other areas of pharmacology (most specifically neuropharmacology) it’s not uncommon for people to need to rotate out of meds in the same class (stimulants, antidepressants) after many years of successful use. Using myself as an example, I did amazing on methylphenidate for adhd for nearly a decade and then it slowly started to lose its efficacy even with dose titration. I eventually switched to generic adderall (different stimulant) and once the dosage was dialed in it has continued to serve me well. I’ve heard from friends and family that this is also a phenomenon in antidepressants for folks with chronic depressive and anxiety disorders. The brain is a bit unique in that it really fights changes from homeostatic baseline and does not like to be perturbed. Luckily we don’t see this effect in our statins or anti hypertensive meds. It was always in the back of my mind that there would be some sort of leveling off with the GLP-1’s (it makes physiological / evolutionary sense). Though as @Ghoul mentioned, the goal of these meds isn’t endless weight loss per se. And while it may be helpful to add / switch from drug to drug, I wonder if maxing out and then adding is a better option?

For me, tirz was an absolute appetite sledge hammer. I switched to Reta after only a week on the 7.5 of tirz and now at 4 mg Reta I can at least get in closer to 3000 calories without any increased cravings or food noise. But I def have saved the tirz in my back pocket for if / when I get up to a high dosage of Reta and need appetite suppression.

For @ChemBB I wonder if there is some genetic polymorphism in terms of how your body handles these compounds in that you get acclimated to them quickly and / or clear them efficiently. Anecdotally for people who are “sensitive” to drugs I find it across the board. That is, those of us who can tolerate grams of gear without serious health effects tend to also be a bit resistant to lower doses of other drugs. Some people’s bodies are just like Sherman tanks in that regard. And of course, what we don’t know about the pharmacokinetics of these drugs can (does) fill a book when you get to N=1.

When you look at bodybuilders over the decades, it’s really quite remarkable the extent to which they’ve had to game their already genetically gifted physiologies to get into contest shape. Carb cycling, severe depletion, lots of trenbolone, metabolic accelerators, etc. At the End of the day, whether we deploy GLP-1’s or not, physique competitors are driving uphill against evolution, trying to maximize muscle while also minimizing fat. It requires a complete hack of normal physiology and it doesn’t last long (hence why even the best bodybuilders sometimes show up flat / spilled over).

 

[Ghoul]

In other areas of pharmacology (most specifically neuropharmacology) it’s not uncommon for people to need to rotate out of meds in the same class (stimulants, antidepressants) after many years of successful use. Using myself as an example, I did amazing on methylphenidate for adhd for nearly a decade and then it slowly started to lose its efficacy even with dose titration. I eventually switched to generic adderall (different stimulant) and once the dosage was dialed in it has continued to serve me well. I’ve heard from friends and family that this is also a phenomenon in antidepressants for folks with chronic depressive and anxiety disorders. The brain is a bit unique in that it really fights changes from homeostatic baseline and does not like to be perturbed. Luckily we don’t see this effect in our statins or anti hypertensive meds. It was always in the back of my mind that there would be some sort of leveling off with the GLP-1’s (it makes physiological / evolutionary sense). Though as @Ghoul mentioned, the goal of these meds isn’t endless weight loss per se. And while it may be helpful to add / switch from drug to drug, I wonder if maxing out and then adding is a better option?

For me, tirz was an absolute appetite sledge hammer. I switched to Reta after only a week on the 7.5 of tirz and now at 4 mg Reta I can at least get in closer to 3000 calories without any increased cravings or food noise. But I def have saved the tirz in my back pocket for if / when I get up to a high dosage of Reta and need appetite suppression.

For @ChemBB I wonder if there is some genetic polymorphism in terms of how your body handles these compounds in that you get acclimated to them quickly and / or clear them efficiently. Anecdotally for people who are “sensitive” to drugs I find it across the board. That is, those of us who can tolerate grams of gear without serious health effects tend to also be a bit resistant to lower doses of other drugs. Some people’s bodies are just like Sherman tanks in that regard. And of course, what we don’t know about the pharmacokinetics of these drugs can (does) fill a book when you get to N=1.

When you look at bodybuilders over the decades, it’s really quite remarkable the extent to which they’ve had to game their already genetically gifted physiologies to get into contest shape. Carb cycling, severe depletion, lots of trenbolone, metabolic accelerators, etc. At the End of the day, whether we deploy GLP-1’s or not, physique competitors are driving uphill against evolution, trying to maximize muscle while also minimizing fat. It requires a complete hack of normal physiology and it doesn’t last long (hence why even the best bodybuilders sometimes show up flat / spilled over).

In terms of "tolerance", GLP, GIP, Glucagon are incretin hormones, produced naturally, and this class of meds is simply exogenous supplementation.

In bariatric surgery, it's not the physical reduction of stomach size that causes weight loss, it's the resulting increased pressure in the intestines, making the tissue stretch and resulting increased GLP activation

Does a tolerance develop to Testosterone in TRT? Estrogen in female hormone replacement? Thyroid hormones? To Insulin, another incretin hormone? (insulin resistance is not "tolerance" and has other causes than normal levels of insulin.

Perceived appetite suppression goes down at a given dose as weight goes down and stops completely once whatever weight level that dose is setting for the metabolic homeostasis weight is reached. If, at the same dose, weight increases beyond the new "weight thermostat" setting for a given dose, appetite suppression returns. But it's not tolerance, that needs to be overcome by takings break or switching. compounds, it's an increase in dose, which pushes the homeostatic weight level lower, and appetite suppression returns until that weight is reached.