Giant Semaglutide Thread (and other GLP-1 / GIP agonists)

Tirzepatide is a wild one. Even 2 weeks after my last dose I have appetite suppression.

Does anyone know how long it takes before Tirzepatide gets out of your system and when the slow gastric emptying stops?
Seems to depend on the person- some people find it wears off soon enough that they need to split their dose into 2 shots a week. Sema does have a longer half-life but I took a break from it for the holidays and was still feeling the appetite suppression after 2 weeks. This is at the lowest dose also- was on for 6wks and never felt the need to increase.
 
Less, I had to use 4mg of Reta to get the suppression I had on 2.5 mg of tirz. 2.5 mg is the lowest starting dose for tirz, 4 mg is on the higher end for starting doses of Reta.
That's comparing on a mg/mg basis, but that isn’t how we define the efficacy of different drugs.

Etc. for tirz for 1 mg only a frag is used as an antagonist on the GL-1 receptor, so you need more mg's ... but at optimal dose it works much better.

Etc. on Mounjaro, officially you start on 2,5 mg, then move up to 5 mg for at least 4 weeks, then 7,5 mg, 10 mg, 12,5 mg all the way up to 15 mg. This is the official guidelines.

For Wegovy you start at 0,25 mg, 0,5 mg, 1 mg, 1,7 mg and ends up at a MAX of 2,4 mg.

So you should rather compare when Tirz is dosed about 6,25 x as high dosed as Sema.

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Still great with the info though: that Tirz is more efficient than Reta (cheaper even) on a mg. to mg basis - though the same explanation as above still goes though.

I wonder how does 2.5 mg tirs compare to 0.5 sema or 1 mg of sema?
 
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That's comparing on a mg/mg basis, but that isn’t how we define the efficacy of different drugs.

Etc. for tirz for 1 mg only a frag is used as an antagonist on the GL-1 receptor, so you need more mg's ... but at optimal dose it works much better.

Etc. on Mounjaro, officially you start on 2,5 mg, then move up to 5 mg for at least 4 weeks, then 7,5 mg, 10 mg, 12,5 mg all the way up to 15 mg. This is the official guidelines.

For Wegovy you start at 0,25 mg, 0,5 mg, 1 mg, 1,7 mg and ends up at a MAX of 2,4 mg.

So you should rather compare when Tirz is dosed about 6,25 x as high dosed as Sema.

-------

Still great with the info though: that Tirz is more efficient than Reta (cheaper even) on a mg. to mg basis - though the same explanation as above still goes though.

I wonder how does 2.5 mg tirs compare to 0.5 sema or 1 mg of sema?
I think it’s fair to roughly compare Tirz and Reta on a mg for mg basis for general, broscientific purposes. They both have around the same maximum dose. Clinically, comparing the effects of the minimum dose of Tirz and a non-minimum dose of Reta is fitting imo, as the starting dose of Tirz produced around the same suppression as a non-minimum dose of Reta. This comparison is only for subjective effects, not the proportions of GLP. GIP and Glucagon agonism.
 
I think it’s fair to roughly compare Tirz and Reta on a mg for mg basis for general, broscientific purposes. They both have around the same maximum dose. Clinically, comparing the effects of the minimum dose of Tirz and a non-minimum dose of Reta is fitting imo, as the starting dose of Tirz produced around the same suppression as a non-minimum dose of Reta. This comparison is only for subjective effects, not the proportions of GLP. GIP and Glucagon agonism.
Yeah, if the subscribed does are the same.
But I think Reta spread it selv over 3 different receptors.
It seems Lilla is trying to fix the way activating the GIP pathway increases Glucagon in Tirz, but adding in a Glucagon agonism as well.

Obviously SEMA does not have that "problem" because it only activates GL-1 ... but it also misses out allot of positive effects from activating GIP (at least in theory ... not even sure about the studies, they are mostly adlibitum eating but suggested a healthy diet - where we will push the kcal deficit)

And you are right to us, the subjective effects vs. price vs. side effects: is what really matters to most of us anyway...

I havn't been on any of it yet, I'm trying to pick one of them to support my RFL diet and lifting though ... I need to supress loads of hunger, but at the same time it would be nice not to crash entirely.
 
How long should you stop using it to have the effects again on a low dose?
Is there any evidence that it desensitizes the receptors significantly?
Because I haven't seen any.

In the studies the need for more mg's correlates with the weight lost, hence the lower kcal intake needed to lose more weight.

Or said differently the mg seems to correlate with the kcal deficit.

My thoughts: If they desensitized the receptors, so would food ... after eating at the same kcal intake for months, we would no longer get satisfied from it: that does not seems to be the case.

We don't need to stop eating for months once in a while to reeset our receptor sensitivity to food.

Now obviously there is extreme cases like anorexia and overeaters and such ... but those these gl-1 mechanisms and such seem more effected to things like trauma and stress, than changes in receptor sensitivity.

Than again it is possible to train an appetite by eating allot for a long time, could be receptors becomming less sensitive.
 
Yeah, if the subscribed does are the same.
But I think Reta spread it selv over 3 different receptors.
It seems Lilla is trying to fix the way activating the GIP pathway increases Glucagon in Tirz, but adding in a Glucagon agonism as well.

Obviously SEMA does not have that "problem" because it only activates GL-1 ... but it also misses out allot of positive effects from activating GIP (at least in theory ... not even sure about the studies, they are mostly adlibitum eating but suggested a healthy diet - where we will push the kcal deficit)

And you are right to us, the subjective effects vs. price vs. side effects: is what really matters to most of us anyway...

I havn't been on any of it yet, I'm trying to pick one of them to support my RFL diet and lifting though ... I need to supress loads of hunger, but at the same time it would be nice not to crash entirely.
That extra energy from Reta will help you a lot. People say Tirz isn’t bad on the tiredness, but I was definitely feeling it. Don’t listen to people that say Reta doesn’t supresss appetite enough. As long as you don’t already have a tolerance built up from other GLPs, it’s gonna do wonders. I had to struggle to get one slice of pizza at my birthday dinner because I had the audacity to eat one chicken wing, a salad, and 3 tiny breadsticks before it came to the table. Lord knows I would have been putting in work on that pizza before Reta, fucker wouldn’t have stood a chance. Now it just dicked me down.
 
That extra energy from Reta will help you a lot. People say Tirz isn’t bad on the tiredness, but I was definitely feeling it. Don’t listen to people that say Reta doesn’t supresss appetite enough. As long as you don’t already have a tolerance built up from other GLPs, it’s gonna do wonders. I had to struggle to get one slice of pizza at my birthday dinner because I had the audacity to eat one chicken wing, a salad, and 3 tiny breadsticks before it came to the table. Lord knows I would have been putting in work on that pizza before Reta, fucker wouldn’t have stood a chance. Now it just dicked me down.
Thank you,

I haven't used any yet ... but are you sure one build a tolerance, that it's not just the diet that takes it toll.

So on RFL you will advice Reta over Tirz over Sema?

How many mg? ... sadly price is a huge factor for me.
 
Source-related discussion is prohibited outside the Steroid Underground subforum.
Thank you,

I haven't used any yet ... but are you sure one build a tolerance, that it's not just the diet that takes it toll.

So on RFL you will advice Reta over Tirz over Sema?

How many mg? ... sadly price is a huge factor for me.
You definitely build tolerance, try to have all your weight loss done within 6 months.

i suggest Tirz or Reta, the side effects of Sema are too high for me to suggest mono use of. Use Tirz if Reta being in phase III trials makes you weary or if you have heart problems. Use Reta if you want the least side effects and an increase in energy instead of a decrease. If exercise performance is important to you, I definitely suggest Reta.

I started Reta on 4mg, and it’s been great for me.

[EDIT: Source-related discussion removed.]
 
Just remembered that I read a trail in Nature on sema where even after 2 years, the participants where still loosing weight:

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial - Nature Medicine

This seems to be a rather solid article on the topic:
Does the effect of weight loss medication wear off over time? - Dr Sue

Thanks for posting that.

Some diet lunatics are citing the weight regain upon GLP-1ra cessation, saying you need to stay on the drugs forever.

"OK bud, do they have to stay on the diet forever?"
 
Thanks for posting that.

Some diet lunatics are citing the weight regain upon GLP-1ra cessation, saying you need to stay on the drugs forever.

"OK bud, do they have to stay on the diet forever?"
I guess it would depend on if they’re the type of person that chose Sema because they won’t maintain a deficit without it, or if they chose Sema because they won’t avoid a surplus without it. These lifelong users should consider what they’ll do every year or so when they inevitably need to take ~3 months off to resensitize their receptors. I’m well aware of the amount of damage that can be done in just a few months.
 
Just remembered that I read a trail in Nature on sema where even after 2 years, the participants where still loosing weight:

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial - Nature Medicine

This seems to be a rather solid article on the topic:
Does the effect of weight loss medication wear off over time? - Dr Sue
Experiences and mileage can vary hugely with these compounds.

I can only speak for myself, but personally Sema was the most potent of the lot for me - both in sides, and in efficacy.
 
Thanks for posting that.

Some diet lunatics are citing the weight regain upon GLP-1ra cessation, saying you need to stay on the drugs forever.

"OK bud, do they have to stay on the diet forever?"
This study is after two years of taking the med though, it shows that as long as you keep taking the druk, you keep your weightloss (on sema), there seems to be no stopping of that effect.

Sadly, on sema at least, almost everyone that stops return to their highest weight within 5 years (it's thought we have a marker in the brain, that will always try to return os to the heaviest weight we have ever been - according to Novo Nordisk).

But it must be possible to make a strategy here to keep the weight off.
Etc. to diet 2 months every year on the drug or something. Personally I'm going to do so everytime I gain a few kg or so of fat ... perhaps using hgh also in some of my time off this drug.

A lot has started to happen after these drugs has been invented, hopefully it's just a matter of time, before they find a way to reset that marker in the brain as well.
Experiences and mileage can vary hugely with these compounds.

I can only speak for myself, but personally Sema was the most potent of the lot for me - both in sides, and in efficacy.
It's interesting because Tirz and Rets effect the GL-1 receptor up to 9 times less mg pr mg ... It's said you need 9 mg og Rets to active the GL-1 as much as 1 mg of Sema ... but Tirz hits another mechanism by being a GIP antagonist as well and SEMA hits at least 4 more mechanisms by hitting 3 receptors in total, including the GL-1, GIP and Glucagon.

Activating GIP should lover side effects allot, it lowers nausea and such.

PS: Not an expert just started to look into these meds, because I'm going on them myself.
 
BTW I wondered if anyone have tried to MIX Rets and Sema? to get more GL-1 activation next to GIP actication ... it's not given to be smart, I know there is many mechanisms that has to be aligned in a very careful 1:1 relation to work in synergy and such .... but still it might be something like that Nova Nordisk is going to do next themselves. 0,5 mg of SEMA with 4 mg of Rets, should be a strong combo.
 
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