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.

 

[Elektrobot]

There isn't any good long term human data on these GLP-1/GIP agonist drugs

You lost me with your first sentence being incorrect. Why are you posting about a topic you are ignorant about?

 

[Billbo98]

You lost me with your first sentence being incorrect. Why are you posting about a topic you are ignorant about?

Because bro that’s the thing all the cool kids are doing now!

 

[bananafeet]

Can we ban this AI stuff from this board.

Sick of arguing with people who think their smart with ChatGPT inspired schizophrenic hallucinations

 

[Endeavor Fitness]

Wow bro you are totally bad ass and amazing.

Yeah taking Retatrutide isn't like those other fatties taking ozempic.

You're ELITE. PART OF THE UPPER CRUST OF SOCIETY.

There's a difference between how fatties use GLPs and how Bodybuilders use them. Fatties want to lose fat, no matter the cost, but end up losing a shit ton of muscle along the way.

They even have a boatload of loose skin, a lot of them. Again, different situations for different subgroups.

 

[riggspersonal]

Why is glucagon accepted here as being inherently muscle sparing? Where did this idea come from? Don’t tell me it’s from DEXA alone.

The evidence that glucagon is in anyway muscle sparing is slim to none. Infusions do lead to minor decreases in RER but this does not account for amino acid breakdown. Obviously it would lower it slightly as substrate for gluconeogenesis is not carbohydrate, so if anything it’s just neutral because any decrease would represent increased fat and protein breakdown while preserving glycogen stores.

Actual benefits of glucagon agonism is a minor increase in expenditure allowing for quicker visceral fat reduction, and minor stimulant effect.

Retatrutide is arguably only preferred over Tirzepatide if you need insulin sensitivity without the appetite suppression, as it is more selective for GIPR over GLP-1R. Any other effect is so minor that it’s probably not worth the increase in RHR and potential cortisol increase from chronic GCGR activation.

If you decide to use it over Tirzepatide you theoretically want to increase protein and reduce carbohydrates, but it’s not really going to matter much imo.

"Muscle sparing" is definitely used too loosely. The bottom line is that both retatrutide and tirzepatide simply make fat a more accessible primary fuel source, meaning the body is less desperate to scavenge amino acids from muscle tissue while in a deficit.

Where retatrutide specifically provides an edge (when dosed high enough for significant glucagon agonism) is by pushing back against metabolic adaptation. As you lose significant mass, your basal metabolic rate inevitably drops, and your body compounds this with adaptive thermogenesis to aggressively conserve energy. Glucagon agonism acts as a counteracting force against this, helping to offset the metabolic crash and keeping your resting energy expenditure elevated by a few hundred calories relative to what it would be otherwise.

That extra headroom makes a massive difference for diet adherence. While it is true that chronic glucagon receptor activation carries a theoretical risk of increased cortisol which is catabolic, the practical dietary advantage is hard to ignore. From a pure numbers perspective, fitting 250g of protein plus enough carbs to preserve glycogen into a 2,100 or 2,200 calorie budget is much more manageable than trying to squeeze it all into an 1,800 or 1,900 calorie budget on a single agonist like semaglutide. So while glucagon is not pharmacologically "muscle sparing" on its own, fighting that metabolic drop provides the mathematical allowance to actually sustain a dietary framework that is.

 

[frenexen]

"Muscle sparing" is definitely used too loosely. The bottom line is that both retatrutide and tirzepatide simply make fat a more accessible primary fuel source, meaning the body is less desperate to scavenge amino acids from muscle tissue while in a deficit.

Where retatrutide specifically provides an edge (when dosed high enough for significant glucagon agonism) is by pushing back against metabolic adaptation. As you lose significant mass, your basal metabolic rate inevitably drops, and your body compounds this with adaptive thermogenesis to aggressively conserve energy. Glucagon agonism acts as a counteracting force against this, helping to offset the metabolic crash and keeping your resting energy expenditure elevated by a few hundred calories relative to what it would be otherwise.

That extra headroom makes a massive difference for diet adherence. While it is true that chronic glucagon receptor activation carries a theoretical risk of increased cortisol which is catabolic, the practical dietary advantage is hard to ignore. From a pure numbers perspective, fitting 250g of protein plus enough carbs to preserve glycogen into a 2,100 or 2,200 calorie budget is much more manageable than trying to squeeze it all into an 1,800 or 1,900 calorie budget on a single agonist like semaglutide. So while glucagon is not pharmacologically "muscle sparing" on its own, fighting that metabolic drop provides the mathematical allowance to actually sustain a dietary framework that is.

100% completely AI. Fuck off bud. You should be banned for this bullshit.

And the 200 calories is not “making or breaking” a diet.

 

[Sampei]

"Muscle sparing" is definitely used too loosely. The bottom line is that both retatrutide and tirzepatide simply make fat a more accessible primary fuel source, meaning the body is less desperate to scavenge amino acids from muscle tissue while in a deficit.

Where retatrutide specifically provides an edge (when dosed high enough for significant glucagon agonism) is by pushing back against metabolic adaptation. As you lose significant mass, your basal metabolic rate inevitably drops, and your body compounds this with adaptive thermogenesis to aggressively conserve energy. Glucagon agonism acts as a counteracting force against this, helping to offset the metabolic crash and keeping your resting energy expenditure elevated by a few hundred calories relative to what it would be otherwise.

That extra headroom makes a massive difference for diet adherence. While it is true that chronic glucagon receptor activation carries a theoretical risk of increased cortisol which is catabolic, the practical dietary advantage is hard to ignore. From a pure numbers perspective, fitting 250g of protein plus enough carbs to preserve glycogen into a 2,100 or 2,200 calorie budget is much more manageable than trying to squeeze it all into an 1,800 or 1,900 calorie budget on a single agonist like semaglutide. So while glucagon is not pharmacologically "muscle sparing" on its own, fighting that metabolic drop provides the mathematical allowance to actually sustain a dietary framework that is.

Something that before was achieved with a lot of cardio, now you can do less cardio and reta will help you maintain a higher calories expenditures leaving more room for tweaking.

Myself I like 5-6mg during a bulk and 10/12mg during a cut. Still undecided where I wanna go during health phase/cruise

 

[madcap71]

I love food and I love eating and as a bodybuilder, I need to get my food down me. Reta allowed me to diet and still eat my meals without any food noise and no issues as I titrated food down. I don't want hardcore appetite suppression as I have enough willpower to diet without a GLP.

 

[riggspersonal]

100% completely AI. Fuck off bud. You should be banned for this bullshit.

And the 200 calories is not “making or breaking” a diet.

ooooookay buddy. you're right about everything, i concede.

 

[Elektrobot]

Some of the most talented and knowledgeable scientists of our time develop a drug called retatrutide, which in series after series of controlled trails is shown to out perform every other medical weight loss treatment on earth

But this guy is even smarter......

Thank you for sharing your decades of experience and research with us. It is literally priceless.

 

[riggspersonal]

Retatrutide is arguably only preferred over Tirzepatide if you need insulin sensitivity without the appetite suppression, as it is more selective for GIPR over GLP-1R.

Also, this is either gross oversimplification, a typo, or complete BS pseudoscience. You're citing receptor sensitiviy but ignoring actual clinical outcome from the phase 2 trials. lower receptor sensitivity in-vitro <=/=> actual clinical effect

 

[bananafeet]

There's a difference between how fatties use GLPs and how Bodybuilders use them. Fatties want to lose fat, no matter the cost, but end up losing a shit ton of muscle along the way.

They even have a boatload of loose skin, a lot of them. Again, different situations for different subgroups.

No there isn't. It's used for appetite control and diet adherence.

You could achieve the same results by take 0.25mg to 0.75mg of semaglutide. At this dose it doesn't shut down the stomach but blunts appetite and controls blood sugar. The ozempic (diabetes drug) dose is 1mg. The fat loss dose (wegovy) is 2.4mg.

It's complete nonsense that you're using the drug differently.

Youre using a weightloss drug developed for morbidly obese people. Not only that you're using the one that has the highest weightloss. IE for the mega fatties.

 

[Billbo98]

No there isn't. It's used for appetite control and diet adherence.

You could achieve the same results by take 0.25mg to 0.75mg of semaglutide. At this dose it doesn't shut down the stomach but blunts appetite and controls blood sugar. The ozempic (diabetes drug) dose is 1mg. The fat loss dose (wegovy) is 2.4mg.

It's complete nonsense that you're using the drug differently.

Youre using a weightloss drug developed for morbidly obese people. Not only that you're using the one that has the highest weightloss. IE for the mega fatties.

100% the Reta cope is a sickness for justifying its use in “Bodybuilders”

 

[bananafeet]

100% the Reta cope is a sickness for justifying its use in “Bodybuilders”

They became the one thing they hated the most.