GIP is not your friend. And why Tirzepatide is superior to Retatrutide

[trev55]

There isn't any good long term human data on these GLP-1/GIP agonist drugs, most of what we know comes from studies on rodents so I'm going to post my thoughts about why some of these drugs may be doing more harm than good, especially in lean, insulin sensitive individuals.
I'll break it into a few parts, and why Tirz is probably much safer and better over the long term than Reta.

1. GIP is not your friend.
GIP isn’t being discussed nearly as much as GLP-1 in fitness contexts, even though many of the newest incretin drugs now deliberately agonize the GIP receptor alongside GLP-1. I want to lay out why I’m not convinced this is automatically a good thing for those who aren't fat as fuck.

Before the current popularity of dual- and multi-agonist drugs — like tirzepatide and retatrutide — GIP was originally dubbed in the literature as the obesity hormone. GIP's normal physiological role after eating is to promote fat storage in adipose tissue.

In white adipose tissue, GIP signaling tends to suppress lipolysis and promote lipid storage, causing increases in white adipose fat mass under caloric excess.

There is evidence in rats that GIP shifts insulin sensitivity in a tissue specific way, reducing insulin sensitivity in muscle, liver and brown adipose tissue, and increasing insulin sensitivity in WAT.

In rodents, CNS GIP signalling has been linked to increased neuroinflammatory signalling, and reduced leptin responsiveness in appetite-regulating centers, so it is eventually de-sensitizing you to the master satiety hormone, a condition seen in obesity.

Finally GIP is described as supporting pancreatic beta-cell proliferation and survival, which is one of the reasons it’s viewed positively in diabetes treatment. However, there is also evidence that chronic overstimulation of the GIP pathway can lead to receptor desensitization and reduced effectiveness over time.

The point is that GIP's role is not a fat loss support hormone, it is a fat storage hormone which makes me question whether strong GIP agonism is helpful or actually harmful for people without existing obesity & insulin resistance.

 

[Country Club Hero]

I’ve used all 3 and determined a while back that I liked Tirz the best. Doesn’t make me feel trashy like Sema but provides way more appetite suppression than Reta. I guess I go by feelz with most things and am usually proven right after science comes out. And I’d be considered fairly lean before using any of them.

 

[gobig2]

so which is best if trying to get your fasted blood glucose down and shed some belly fat? Have horrible sugar cravings at night. A1C is fine but blood glucose always running in the low 100's.

 

[BabaJagga]

i think reta is overhyped by plenty of internet people trying to make profit of selling it. they buy it from china for cheap price, than make videos about how amazing it is, its the best thing in the world etc etc, then sell it with huge profit. they can do that cause its still grey zone. probably cant happen with tirz.

after that internet does its thing and people "parrots" same stuff over and over
"add reta for health"
"add reta to test & gh thats god stack"
"reta this reta that"
meanwhile most of them dont understand these drugs at all and all their knowleage comes from 10 second videos on social media

i think tirz is fine and its very effective. im even happy that people switched to reta mostly and tirz is even cheaper.
sema would work as well but i went for tirz cause it should have less sides. and i have 0
issues.

 

[Dohtem22]

So, what if you have lost a bunch of weight on Tirz and are now in a maintenance phase? Would you stick with high dose tirz or switch to reta?

Congrats on the weight loss… during that time did you learn more about diet and fix your relationship with food? Or are you just going to rely on the drug to “maintain” the rest of your life?

Everyone- “THE OTHER HEALTH BENEFITS THOUGH! “

 

[BabaJagga]

Congrats on the weight loss… during that time did you learn more about diet and fix your relationship with food? Or are you just going to rely on the drug to “maintain” the rest of your life?

Everyone- “THE OTHER HEALTH BENEFITS THOUGH! “

blood sugar control with gh is real.
ive found that slow tappering down works great. agter that just use gear amd bulk

 

[Sampei]

I think you all are missing a massive point on why reta is considered the favourite for most of bodybuilders. Yes you read it correctly: BODYBUILDERS.

not fat ppl, not ex obese with hunger issues that can't manage appetite on a cut for many reasons or whatever other categories you wanna fit in.

BODYBUILDERS aka ppl that when there was no reta sema tirz were able and are still able to diet down to low single digit bodyfat with mostly sheer willpower.

Now if we assume that we are in a bodybuilding forum (aahahahahahaha) and we are all practicing mostly this discipline why is reta the superior substance for a bodybuilder?

Is it that hard to understand?
LOW APPETITE SUPPRESION, exactly you got that perfectly right. A bodybuilder doesn't want and need strong appetite suppression, he wants all the other benefit of the glp-1 family. Higher insulin sensitivity, reduced systemic inflammation, better lipids, better BP etc.
Why? Because it fuckings let them use more GH first of all and optimize every other process BUT it lets them bulk while they maintain better insulin sensitivity and it lets them cut without the massive struggle of crazy hunger.

A REAL bodybuilder will laugh in the face of ppl saying oh but reta doesn't suppress as much as tirz I still want to eat here and there.

Brother these ppl starve themselves down to 5% BF while still training and working the life, do you really think they have issue managing a little less appetit suppression vs when they were doing the same without any appetite suppression at all?

One more thing, tirz gives to many ppl, fatigue, acid reflux, very slow gastric emptiness, a lot of hunger suppression, with amazing insulin sensitivity that... You can't use for shit because you can't slam food on it.

Yes this is the average experience of th average user so ON AVERAGE for a bodybuilder reta is superior.

For any other person it is a matter of choices.

 

[DigD]

There isn't any good long term human data on these GLP-1/GIP agonist drugs, most of what we know comes from studies on rodents so I'm going to post my thoughts about why some of these drugs may be doing more harm than good, especially in lean, insulin sensitive individuals.
I'll break it into a few parts, and why Tirz is probably much safer and better over the long term than Reta.

1. GIP is not your friend.
GIP isn’t being discussed nearly as much as GLP-1 in fitness contexts, even though many of the newest incretin drugs now deliberately agonize the GIP receptor alongside GLP-1. I want to lay out why I’m not convinced this is automatically a good thing for those who aren't fat as fuck.

Before the current popularity of dual- and multi-agonist drugs — like tirzepatide and retatrutide — GIP was originally dubbed in the literature as the obesity hormone. GIP's normal physiological role after eating is to promote fat storage in adipose tissue.

In white adipose tissue, GIP signaling tends to suppress lipolysis and promote lipid storage, causing increases in white adipose fat mass under caloric excess.

There is evidence in rats that GIP shifts insulin sensitivity in a tissue specific way, reducing insulin sensitivity in muscle, liver and brown adipose tissue, and increasing insulin sensitivity in WAT.

In rodents, CNS GIP signalling has been linked to increased neuroinflammatory signalling, and reduced leptin responsiveness in appetite-regulating centers, so it is eventually de-sensitizing you to the master satiety hormone, a condition seen in obesity.

Finally GIP is described as supporting pancreatic beta-cell proliferation and survival, which is one of the reasons it’s viewed positively in diabetes treatment. However, there is also evidence that chronic overstimulation of the GIP pathway can lead to receptor desensitization and reduced effectiveness over time.

The point is that GIP's role is not a fat loss support hormone, it is a fat storage hormone which makes me question whether strong GIP agonism is helpful or actually harmful for people without existing obesity & insulin resistance.

AM I allowed to expose lab selling fake reta in here?

 

[iudex]

LOW APPETITE SUPPRESION, exactly you got that perfectly right. A bodybuilder doesn't want and need strong appetite suppression, he wants all the other benefit of the glp-1 family. Higher insulin sensitivity, reduced systemic inflammation, better lipids, better BP etc.
Why? Because it fuckings let them use more GH first of all and optimize every other process BUT it lets them bulk while they maintain better insulin sensitivity and it lets them cut without the massive struggle of crazy hunger.

Couldn’t you just run lower doses of sema or tirz to capture the metabolic benefits while keeping appetite suppression manageable?

For many users, improvements in insulin sensitivity, lipids, glycemic control, and systemic inflammation (etc.) occur at relatively modest doses. Appetite suppression is dose-dependent, but may only appear at higher relative doses.

That said, some people experience disproportionate appetite suppression or GI side effects even at very low doses. For them, titration may not solve the issue, and a different GLP-1–based agent could make more sense.

So reta isn’t inherently superior. It may simply be a better fit for individuals who find sema or tirz suppress appetite too aggressively at clinically effective doses. If metabolic benefits can be achieved without compromising caloric intake, then in principle any GLP-1 could suffice, no?

 

[crispybacon!]

I think you all are missing a massive point on why reta is considered the favourite for most of bodybuilders. Yes you read it correctly: BODYBUILDERS.

not fat ppl, not ex obese with hunger issues that can't manage appetite on a cut for many reasons or whatever other categories you wanna fit in.

BODYBUILDERS aka ppl that when there was no reta sema tirz were able and are still able to diet down to low single digit bodyfat with mostly sheer willpower.

Now if we assume that we are in a bodybuilding forum (aahahahahahaha) and we are all practicing mostly this discipline why is reta the superior substance for a bodybuilder?

Is it that hard to understand?
LOW APPETITE SUPPRESION, exactly you got that perfectly right. A bodybuilder doesn't want and need strong appetite suppression, he wants all the other benefit of the glp-1 family. Higher insulin sensitivity, reduced systemic inflammation, better lipids, better BP etc.
Why? Because it fuckings let them use more GH first of all and optimize every other process BUT it lets them bulk while they maintain better insulin sensitivity and it lets them cut without the massive struggle of crazy hunger.

A REAL bodybuilder will laugh in the face of ppl saying oh but reta doesn't suppress as much as tirz I still want to eat here and there.

Brother these ppl starve themselves down to 5% BF while still training and working the life, do you really think they have issue managing a little less appetit suppression vs when they were doing the same without any appetite suppression at all?

One more thing, tirz gives to many ppl, fatigue, acid reflux, very slow gastric emptiness, a lot of hunger suppression, with amazing insulin sensitivity that... You can't use for shit because you can't slam food on it.

Yes this is the average experience of th average user so ON AVERAGE for a bodybuilder reta is superior.

For any other person it is a matter of choices.

This is exactly why I switched from Tirz to Reta. While it helped expedite some initial weight loss, it was becoming a chore to get enough calories on Tirz. With Reta, I’m getting all the desired benefits to health markers, along with mild appetite suppression and reduced food noise.

 

[Psy-chonaut]

AM I allowed to expose lab selling fake reta in here?

- > Do it in the 'Analytical lab testing' subforum ....

 

[Sampei]

Couldn’t you just run lower doses of sema or tirz to capture the metabolic benefits while keeping appetite suppression manageable?

For many users, improvements in insulin sensitivity, lipids, glycemic control, and systemic inflammation (etc.) occur at relatively modest doses. Appetite suppression is dose-dependent, but may only appear at higher relative doses.

That said, some people experience disproportionate appetite suppression or GI side effects even at very low doses. For them, titration may not solve the issue, and a different GLP-1–based agent could make more sense.

So reta isn’t inherently superior. It may simply be a better fit for individuals who find sema or tirz suppress appetite too aggressively at clinically effective doses. If metabolic benefits can be achieved without compromising caloric intake, then in principle any GLP-1 could suffice, no?

5mg tirz had me forgetting to eat for close to 12hrs and when eating it was hell.

10mg reta allowed me still to eat quite enough to get fat if i really wanted, 5mg of reta makes me feel like I'm not even on glp1 unless I eat very fatty food

 

[johnjay06]

I use reta because
1. The Triumph trials running now show that it may help kidney function and I need that
2. As Sampei said, I don't hate food on it. Tirz made me want to stop eating and doing that made me flat and feel like shit
3. It helps with blood sugar control from HGH, although I am on a break from HGH right now


And I see some references to Ghoul in here, he used ai for most of his responses, so you can get any info that he used easily on your own.

 

[riggspersonal]

I'm on 5mg/week of reta right now and eating at clean maintenance. I find the appetite suppression manageable. Any more and it would make it unpleasant to get my calories and macros in.

One of the biggest strikes against reta for me is the increase in resting heart rate. My dosage is right at the level where I'm getting material effect from glucagon agonism. Think of it like a dimmer switch where up to 4mg is pretty much unusable light but above that it's usable. My RHR has increased anywhere from 10 - 15% depending on the day. I've seen others get up to a 20% increase in RHR.

For someone running a relatively standard stack of PEDs long term such as HGH, testosterone, and reta, it's a fkn land, sea, and air attack on your heart if you're not managing things effectively.

HGH can increase fluid retention and blood pressure
Testosterone can increase RBC count and blood thickness (erythrocytosis)
Retatrutide can increase resting heart rate and importantly the FORCE of myocardial contractility. Faster + harder.

Obviously most of us who are serious about our health are taking proper interventions to manage these things, but there is still incremental increased stress load across these pillars regardless. We're asking our hearts to work harder by having it pump thicker blood, faster, at a higher pressure - a cardiovascular triad of risk. Over the long term, not doing any favors to prevent LVH.

 

[BP_6]

Saying activating GIP is a good or bad thing is much too complex to say one way or another. Apparently, the two current best GLP series drugs both act as an agonist.

Some upcoming drugs don't touch it, or even try to act as an antgaonist. The one antganoist one they are having issues with due to what the FDA is saying are unaceptable nausea levels more or less. So part of the reason I am sure for the agonist is it seems to act as an anti-nausea which seems to occur with GLP-1 activation.

Summary, it is a complex topic and one I am leaving to the scientist who actually understand these complex mechanisms.

 

[Mfras]

@Sampai that’s the response I was waiting to read!

I started reta at 2mg and I’m up to 5mg split tues/fri. I noticed ≈2 days of hunger affects the whole time, right after going from 2.5 to 4mg. I control food by tracking cals & macros because although breakfast is the same every day and PWO carbs are also the same those 5 days out of the week, I like a small amount of variety so all my eating isn’t robotic.

I’m not a BODYBUILDER who just eats the same rice, chicken, greens every day but I live a bodybuilding lifestyle in a lot of ways. That includes pinning GH AM/PM and I’m confident reta offsets some of the metabolic sides of that. Any extra fat mobilization is the cherry on top, and I’ll happily trade fighting some hunger if I stay up too late for the ability to eat and enjoy food, even on a somewhat restrictive 2000 cals in my current cut.

I understand tirz as an elegant solution for average fat people that want to be skinny fat, and have come to understand it as a helpful tool for real bodybuilders who are miserable and starving at 6,7,8% fat chasing that christmas tree and cross striations, but it ain’t for me.

 

[liftlurker]

I personally have had great experiences with Reta. In all honesty we don’t know the effects of any GLP’s long term.

I think it’s splitting hairs at a certain point. I mean I’m still having an easy time sticking with my diet, but not under-eating like many are reporting on tirzepatide. The results of the control studies seem be promising.

At the end of the day, you’ll choose what fits into your goals. I personally don’t take Tren anymore because of unknown neurotoxicity, poor sleep, heartburn, metabolic effects, etc. Some people swear by it though

 

[riggspersonal]

I personally have had great experiences with Reta. In all honesty we don’t know the effects of any GLP’s long term.

I think it’s splitting hairs at a certain point. I mean I’m still having an easy time sticking with my diet, but not under-eating like many are reporting on tirzepatide. The results of the control studies seem be promising.

At the end of the day, you’ll choose what fits into your goals. I personally don’t take Tren anymore because of unknown neurotoxicity, poor sleep, heartburn, metabolic effects, etc. Some people swear by it though

We can surmise some of the long-term effects by what is happening in the short-term though, such as the impact on your heart rate and pump force.

 

[Duraclear]

I appreciate the OP for introducing this topic and stirring up some debate. I'm very new to these particular substances, so I appreciate all of this discussion.

I recently started reta mainly because 3 agonisms more gooder than 2! But also as some others have mentioned, I don't need my appetite crushed in the way I consistently hear that Tirz does. I already fast regularly and haven't eaten a grain of processed sugar in years, so will power isn't an issue. However, I have very stubborn visceral fat and high fasted glucose (90s) despite all of my best unassisted efforts.

At even the 1.5mg of reta that I am on now as I titrate, the appetite suppression is just right. Makes fasting less of a grind, and I can still eat when I need to. I am also definitely noticing more definition in my abs after only two weeks. I'm interested to see what it does to my labs in a couple of months.

 

[riggspersonal]

This is pretty thought provoking to me as someone that has exclusively taken retatrutide. If I was taking lower than 4mg/week, I don't think I'd see any reason to take reta over tirz.

For reta: At 4mg and above, you're working the "calories out" side of the equation and can actually eat more because your basal metabolic rate and resting energy expenditure are higher, hence the increase in RHR. Glucagon is also actively signaling the body to break down stored glycogen and mobilize triglycerides (fat) for energy. This can clear liver fat in weeks, something that is prized by individuals running oral steroids or other hepatotoxic compounds.

So you can eat more while cutting and clear liver fat IF your dosage is high enough to activate glucagon component in a material way. And this is where the quoted "muscle sparring" benefits come from as your appetite isn't so suppressed vs something like tirz or semaglutide where it can be difficult to hit your protein targets and get enough carbs to where your muscle's glycogen stores aren't depleted.

All that said, I think it's very individualized as to which drug is the best choice for you. It's definitely not one size fits all.