MESO-Rx
Anabolic Steroids
Giant Semaglutide Thread (and other GLP-1 / GIP agonists)
- Thread starter Doodle
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egruberman
Well-known Member
That's funny, because I posted several studies that demonstrated that the development of the frontal lobe went well into the mid 20s. These studies were based on MRI data among other things and had nothing to do with cognition. Further, you were the person that extrapolated that to mean that it should represent an excuse for otherwise unacceptable behavior. It's a straw man and as is so often the case, you failed to directly address the argument in question.
It seems reasonable that most men would find youthful, sexually mature individuals to be physically attractive, but attraction is much more than that. I wouldn't find most 20-somethings attractive because they tend to lack emotional maturity and very few of them know how to fuck very well.
I challenged you before and will do it again. Please provide real, actual evidence of this that's not an opinion piece. I've personally scoured the literature at length and could find nothing contradictory.
iris
Well-known Member
Nah, it’s for everyone. I am just refreshing anyone new who hasn’t monitored the whole thread and the original post
Fair enough.
Sorry I assumed different intentions
❤
IronMetal_2
Member
Lets just wait until Amgen provides more details on their MariTide peptide which supposedly is injected only once a month or even less frequent...
Ghoul
Well-known Member
4mg is the closest equivalent, just slightly stronger than 5mg Tirz. 4 weeks to stable plasma level and maximum effect, then either increase or continue to plateau before titrating to 8, then 12, if desired.
If you stay on 12 as a maintainance dose, there's no going back to Tirz without having to exceed the current max approved dose. At any lower dose of Reta you can switch back.
This is assuming you want to adhere to the protocol Eli Lilly settled on.
Wow that was detailed. Thank you.
What about people that add in some ozempic to hammer glp1 while maintaining lower dose of reta or tirz? Is that a good strategy or is that just bro science?
Ghoul
Well-known Member
It's both bro science and effective, but not at what I consider an acceptable cost, and any added effectiveness may not be durable.
I would not pile on another compound without hitting the limits of one first.
Sometimes I wonder if these people are 500 pounds, because it's far too many to be in the tiny group the standard protocols, thoroughly tested at the cost of hundreds of millions, in trials involving 15,000+ subjects, are ineffective for.
They seem to think these things are designed not by teams of hundreds of hardcore scientists balancing hundreds of critical factors, but just casually put together, and they can easily come up with a better plan. Yes, some things are chosen for business reasons, like "we can have an interval between 5.5 and 8.5 days with similar results, with 6.25 days being ideal" and 7 is picked for convenience, but only within the range of what's been proven to have the best outcomes, including risks.
99.9% of these clowns couldn't tell you how they decide what ratio to dilute with BAC, other than personal preference, or that it makes any difference. It makes ALL the difference, and picking wrong could permanently impact the effectiveness not only of the specific drug, but others in the same class, and even whether your natural versions of the same hormones, GLP, GIP, and Glucagon in the case of Reta, continue to work properly, an effect called "cross immunogenicity" that could be lifelong.
The FDA says "show us this doesn't happen with your proposed retail formulation" before approving, and pharma does, because they know they have to. The FDA doesn't say "show us this doesn't happen at 4x the concentration just in case some guy on reddit decides he wants to make his 12mg dose fit in a tiny .3 ml syringe" or, "what if someone mixes a little Sema in? Will the peptides adhere at any point in the amino chain creating a molecule that sets off warning signals to the immune system so it creates antibodies neutralizing natural GIP hormones and sets the patient up to be 10 times as vulnerable to serious fatty liver disease in a few years?".
See what I mean?
I'd stick to the demonstrably safe path of one compound until you hit its limits. Knowing there's a built in safety buffer, I'm not really bothered going 10-20% higher in dosing if necessary. I'd only add another compound if there were no other option, never in the same syringe, not on the same day, and certainly not to save a few bucks and risk turning my body into a petri dish ending up the subject of some pHD's thesis a few years from now about how things can go terribly wrong from superficially harmless experimentation with these incredibly complex molecules.
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HB_22
Well-known Member
Oh really? Coming from you, the one on glp-1 drugs for 7 years and barely doing 200 steps a day while sitting in your mom's basement all day is wondering?
Ghoul
Well-known Member
Precisely the kind of retard mentality that thinks GLPs are "diet pills" in a syringe.
Do you think the people on stable maintainance doses just keep losing weight, month after month?
Hasn't had anything to do with weight loss for years, but all the other benefits this class of hormones provide in terms in terms of heart, liver, brain, and neurological health irrespective of weight.
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HB_22
Well-known Member
Nice try. My point was that you were still morbidly overweight, in other words a fat fuck, still after 7 years of abusing glp-1 drugs and meth sitting in your mom's basement copying ChatGPT messages all day and night. And yes people keep losing weight even on maintenance doses, but they do put in the work. Something you dont do as you are too lazy.
Ghoul
Well-known Member
I don't use ChatGPT at all, and you don't know anything about me or what "work" i put in. All you're doing is repeating mindless insults, like a high school kid trying to fit in with some bullies.
Look man, my point was that the standard protocols are demonstrably safe, and effective for the overwhelming majority of people.
Deviating carries significant risks because of factors most aren't aware of, and there's good reason to believe we're seeing them start to appear.
Unless you're in the minuscule group the proven protocols don't work for (like you're 500lbs and 30% weight loss isn't enough), I don't see any good reason to take those risks, and worse, the people promoting these deviations don't mention any of the potential downsides either.
There are two types of people in a conversation about issues like this. Those who seek to expand knowledge, and those who seek to diminish.
Don't be the latter. Challenge any of my assertions and I'm happy to listen in good faith, maybe you'll make a good point and I'll change my position. I welcome that, but all you're doing is making ad hominem attacks and dragging this thread down.
Ghoul
Well-known Member
Some have reported 30. 20 is almost certainly well within the "safety" buffer.
15 is the max "official" clinically tested dose whether you're 40kg or 200kg, so they're clearly not taking body size into account, and almost all drugs are dependent on mg/kg. I'd definitely go higher Tirz before considering "stacking" though, and only if you genuinely plateaued.
Remember it takes four weekly doses to reach max effect of any dose. That's when blood plasma concentration stabilizes.
At least for GLP receptors, it appears the proportion activated determines effectiveness for weight regulation. Size=more receptors. Males have a much higher density of GLP receptors, which probably accounts for the lesser effectiveness of these drugs clearly seen in men (no one in medicine seems to give a shit). It'll be some time before we see custom, precision dosing of GLPs, and all the other meds that work in similar fashion in medicine, unfortunately.
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Trenbolonetax
Well-known Member
Yes
I have. I’m finding more success with 12mg Reta.
Captainpotatohead
Member
I was under the impression tirz was better for appetite suppression than Reta? I get a bit apprehensive about switching to Reta after reading the issues people seem to have with their heart rates increasing etc
egruberman
Well-known Member
My understanding is that reta has a greater binding affinity to GLP1 and GIP than tirz, in addition to the glucagon effect.
Semaglutide has a much greater binding affinity to GLP1 than tirzepatide and retatrutide. Theoretically then, one could add it in to a stack, but there are potential downsides to this and nothing in the literature that supports it. As @Ghoul stated, it's probably best to stick with a single compound for as long as its effective, which for most, should be indefinitely.
Peter Attia just did an AMA on GLP-1 agonists:
#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape - Peter Attia
"If you're taking these drugs, really, really pay attention to your protein consumption and your resistance training. . .that's obviously going to be an important part of being on the right side of that body composition curve.” — Peter Attia
peterattiamd.com
It's an interesting summary of the literature. The only point that I found particularly interesting was that there is no evidence (according to him) of any health benefit of a GLP1 agonist independent of the effect on body composition and metabolic improvements.
Some other points:
There's more safety data and nothing to suggest any issues with these compounds.
Most likely they should be taken indefinitely and there's no real observed reduction in efficacy, provided they aren't used intermittently.
He points to the SELECT trial which shows no weight regain with semaglutide when continued over the course of four years:
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial - Nature Medicine
A prespecified analysis of the SELECT trial revealed that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo and showed improvements in various anthropometric indices.
www.nature.com
There's some other stuff in there. It's a good listen if you have a subscription, but I think nothing that would surprise any of us.
Trenbolonetax
Well-known Member
I
would really like to get the binding affinity for each nailed down on a relative basis to one another. Feel like I saw it somewhere but could never find it again.My understanding is that reta has a greater binding affinity to GLP1 and GIP than tirz, in addition to the glucagon effect.
Semaglutide has a much greater binding affinity to GLP1 than tirzepatide and retatrutide. Theoretically then, one could add it in to a stack, but there are potential downsides to this and nothing in the literature that supports it. As @Ghoul stated, it's probably best to stick with a single compound for as long as its effective, which for most, should be indefinitely.
Peter Attia just did an AMA on GLP-1 agonists:
#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape - Peter Attia
"If you're taking these drugs, really, really pay attention to your protein consumption and your resistance training. . .that's obviously going to be an important part of being on the right side of that body composition curve.” — Peter Attia
It's an interesting summary of the literature. The only point that I found particularly interesting was that there is no evidence (according to him) of any health benefit of a GLP1 agonist independent of the effect on body composition and metabolic improvements.
Some other points:
There's more safety data and nothing to suggest any issues with these compounds.
Most likely they should be taken indefinitely and there's no real observed reduction in efficacy, provided they aren't used intermittently.
He points to the SELECT trial which shows no weight regain with semaglutide when continued over the course of four years:
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial - Nature Medicine
A prespecified analysis of the SELECT trial revealed that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo and showed improvements in various anthropometric indices.
There's some other stuff in there. It's a good listen if you have a subscription, but I think nothing that would surprise any of us.
egruberman
Well-known Member
Units are nanomolars, lower is better. The relative percentages are hard to express, but <1 is "high" 1-100 is "moderate" and >100 is "low".
Source for sema:
Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide - PubMed
Liraglutide is an acylated glucagon-like peptide-1 (GLP-1) analogue that binds to serum albumin in vivo and is approved for once-daily treatment of diabetes as well as obesity. The aim of the present studies was to design a once weekly GLP-1 analogue by increasing albumin affinity and secure...
pubmed.ncbi.nlm.nih.gov
Imma skip the others for now unless anyone cares. Much of this data is non-specific and proprietary.
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UncleBuns
Well-known Member
Great information. Thanks for sharing!View attachment 298482
Units are nanomolars, lower is better. The relative percentages are hard to express, but <1 is "high" 1-100 is "moderate" and >100 is "low".
Source for sema:
Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide - PubMed
Liraglutide is an acylated glucagon-like peptide-1 (GLP-1) analogue that binds to serum albumin in vivo and is approved for once-daily treatment of diabetes as well as obesity. The aim of the present studies was to design a once weekly GLP-1 analogue by increasing albumin affinity and secure...
Imma skip the others for now unless anyone cares. Much of this data is non-specific and proprietary.
Ghoul
Well-known Member
My understanding is that reta has a greater binding affinity to GLP1 and GIP than tirz, in addition to the glucagon effect.
Semaglutide has a much greater binding affinity to GLP1 than tirzepatide and retatrutide. Theoretically then, one could add it in to a stack, but there are potential downsides to this and nothing in the literature that supports it. As @Ghoul stated, it's probably best to stick with a single compound for as long as its effective, which for most, should be indefinitely.
Peter Attia just did an AMA on GLP-1 agonists:
#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape - Peter Attia
"If you're taking these drugs, really, really pay attention to your protein consumption and your resistance training. . .that's obviously going to be an important part of being on the right side of that body composition curve.” — Peter Attia
It's an interesting summary of the literature. The only point that I found particularly interesting was that there is no evidence (according to him) of any health benefit of a GLP1 agonist independent of the effect on body composition and metabolic improvements.
Some other points:
There's more safety data and nothing to suggest any issues with these compounds.
Most likely they should be taken indefinitely and there's no real observed reduction in efficacy, provided they aren't used intermittently.
He points to the SELECT trial which shows no weight regain with semaglutide when continued over the course of four years:
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial - Nature Medicine
A prespecified analysis of the SELECT trial revealed that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo and showed improvements in various anthropometric indices.
There's some other stuff in there. It's a good listen if you have a subscription, but I think nothing that would surprise any of us.
My understanding is that reta has a greater binding affinity to GLP1 and GIP than tirz, in addition to the glucagon effect.
Semaglutide has a much greater binding affinity to GLP1 than tirzepatide and retatrutide. Theoretically then, one could add it in to a stack, but there are potential downsides to this and nothing in the literature that supports it. As @Ghoul stated, it's probably best to stick with a single compound for as long as its effective, which for most, should be indefinitely.
Peter Attia just did an AMA on GLP-1 agonists:
#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape - Peter Attia
"If you're taking these drugs, really, really pay attention to your protein consumption and your resistance training. . .that's obviously going to be an important part of being on the right side of that body composition curve.” — Peter Attia
It's an interesting summary of the literature. The only point that I found particularly interesting was that there is no evidence (according to him) of any health benefit of a GLP1 agonist independent of the effect on body composition and metabolic improvements.
Some other points:
There's more safety data and nothing to suggest any issues with these compounds.
Most likely they should be taken indefinitely and there's no real observed reduction in efficacy, provided they aren't used intermittently.
He points to the SELECT trial which shows no weight regain with semaglutide when continued over the course of four years:
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial - Nature Medicine
A prespecified analysis of the SELECT trial revealed that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo and showed improvements in various anthropometric indices.
There's some other stuff in there. It's a good listen if you have a subscription, but I think nothing that would surprise any of us.
It's unfortunate but not surprising to keep hearing "tolerance" and " stopped working", the diet pill mentality applied to this class of compounds when it's clear that's nearly non existent. If a permanent reduction in effectiveness results from all the "techniques" to "overcome tolerance" based on the reckless advice being spread it'll border on tragic.
As far as evidence of health benefits independent of metabolic and weight improvements, it's ample, particularly in vitro and animal studies.
A major limiting factor up to now is many of the benefits are discovered in trials that haven't included normal weight participants.
There are a few off the top of my head. Atrial structure improvement, that is the reversal of long term damage from stresses, is pronounced in normal weight, non-diabetics but not the obese.
Phase II trials to approve Semaglutide for treating alcohol use disorder have been very successful, an effect entirely independent of BMI.
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