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

[Doodle]

Wanted to create a thread where everyone can post their experiences with different sourced Semaglutide.

Who are you using?
Pharma vs non?
Dosage?
How long have you been taking it?
What are your thoughts?
Have you lost weight?
Side effects?
Oral vs injection?
Tests?

 

[Ghoul]

Thanks for your help. I might mess with it more and try other things to see if anything makes it better or worse.

Please share the results of whatever you discover through your experiments.

One other thing. Perhaps try .2um filtering the solution causing the reaction if you can and see if it's still doing it. I wonder if that vial developed aggregates for some reason and the other didn't. A tiny amount of silicon could cause that.

 

[Juiced_lizard]

Please share the results of whatever you discover through your experiments.

One other thing. Perhaps try .2um filtering the solution causing the reaction if you can and see if it's still doing it. I wonder if that vial developed aggregates for some reason and the other didn't. A tiny amount of silicon could cause that.

Used a new vial - diluted to .5ml and no issues. Same bac water. Maybe that vial is off in some bit.

 

[Juiced_lizard]

This might be a self explanatory answer here but on the theory of proper dilution ratios. Should you dilute the peptide in the 3ml vial it comes in and then transfer to a sterile let’s say 10ml vial and add the proper amount of bac water into that vial?

 

[Ghoul]

This might be a self explanatory answer here but on the theory of proper dilution ratios. Should you dilute the peptide in the 3ml vial it comes in and then transfer to a sterile let’s say 10ml vial and add the proper amount of bac water into that vial?

If necessary to get the correct dilution ratio, and consider filtering during the transfer,

It's even better to use smaller dose vials, so it spends as little time as possible in reconstituted form. Sometimes there's little to no per milligram price difference for smaller dosed vials, other times it's a huge premium, so you have to make that call on a case by case basis.

 

[AlexDavis43]

It spends the same time reconstituted if you reconstitute 1 mL into 10 vials or 10 mL into 1 vial. He's not dividing up the lyophilized powder into separate vials.

 

[Ghoul]

It spends the same time reconstituted if you reconstitute 1 mL into 10 vials or 10 mL into 1 vial. He's not dividing up the lyophilized powder into separate vials.

I'm talking about buying lower dosed vials.

 

[unid888]

If you're planning to go back on, I'd really suggest you stay on a low maintainance dose.

There is no tolerance that develops over time. These drugs are designed to be used like insulin for diabetics. Some degree of "immunogenicity", that is, the immune system learning how to quickly attack and remove the compound from your system develops, and when you take an extended break, and come back, it only strengthens this unwanted effect, potentially making it completely ineffective eventually. It may be short lasting, or permanent immunity depending on the specific GLP compound. No one knows, other than Liraglutide, for instance, seems to make you immune to Tirzepatide for years, at least, after stopping.

Sema antidrug antibodies don't affect Tirz, apparently. However, if you develop Sema antibodies, they will attack NATURAL GLP, which helps explain why the "rebound" for some quitters results in them gaining even more weight, as their own GLPs can't suppress appetite as much as they would before. That's a huge risk imo.

By staying on, the body seems to tolerate its presence without increasing its immune response,

There are NO downsides to continuous use, only proven health benefits. You're very modestly supplementing the level of naturally present hormones produced by the digestive system.

This is why I reccomend people consider cost per dose of continuous use when choosing which to use.

If a small dose of Reta is too costly, hopefully Tirz will do the trick, as it's molecule is very close to Reta in shape, I mean 2.5mg Tirz a week is around $2 I think, and it's still enough to keep hitting those GIP receptors in your liver, clearing fat out, and undoing years of scar buildup.

If there's no tolerance buildup, why do people even need to increase to 2.4mg sema dose? Why don't we all stay at 0.75mg? What makes the drug less effective over time?

Do you know the difference in the chance of developing an immune response when taking a 1x weekly vs. 3x weekly dosage?

Does prolonged use at the same dose increase the chances of immune response?

Does a higher dosage increase the chance of immune response?

I'm only asking because I've tried doing one shot of 0.25mg, and 0.5mg just to see how I'd react to the drug (didn't feel it at all) and switched to 0.25mg MWF protocol the other time which started working that same week.

My idea is that if you can peak less, get fewer potential sides and faster benefits so you can use it for shorter durations and overall it's more convenient to get a faster effect instead of building up for weeks.

 

[rexy]

If there's no tolerance buildup, why do people even need to increase to 2.4mg sema dose? Why don't we all stay at 0.75mg? What makes the drug less effective over time?

I'm not an expert on these and Ghoul will know better, but I assume the ramping up of dose is not because of tolerance developing in the sense of adapting to it and it not working, but more so to gradually assess your tolerance to the side effects at given doseages before diving in. And also because you don't know what dose is needed to achieve your ideal lowered 'set point' via GLP agonists.

if you look at the blood levels, 0.25 over 4 weeks builds to just under 0.5 before the 5th injection. Then you take 0.5 and 4 weeks of that leads to almost 1mg blood levels before you take 1mg. So the dose increases tie in with where blood levels are sat. It was obviously designed to do that when looking at how the levels line up prior to dose changes when injecting 1x per week.

To me, it looks like the drug designers were looking for ways to test sensitivity and create a naturally ramping dosing schedule, seeing as Sema sides can be harsh.

And also, the dose change is because the dose of 0.75mg - or any given dose - doesn't achieve the same results, nor a low enough 'set point' reset, for everyone. Many people targeted with this drug are morbidly obese - it's different if you're using it already reasonably lean to make dieting easier to 8%.

Seeing as you didn't get any side effects, the faster build up was clearly fine for you and so worked out. But I think the dosing schedule was set up the way it was, alongside the pharmakinetics of the drug, to factor in that the majority may have harsh impact of a sudden onset of GLP agonism - especially in the obese.

 

[Ghoul]

If there's no tolerance buildup, why do people even need to increase to 2.4mg sema dose? Why don't we all stay at 0.75mg? What makes the drug less effective over time?

Do you know the difference in the chance of developing an immune response when taking a 1x weekly vs. 3x weekly dosage?

Does prolonged use at the same dose increase the chances of immune response?

Does a higher dosage increase the chance of immune response?

I'm only asking because I've tried doing one shot of 0.25mg, and 0.5mg just to see how I'd react to the drug (didn't feel it at all) and switched to 0.25mg MWF protocol the other time which started working that same week.

My idea is that if you can peak less, get fewer potential sides and faster benefits so you can use it for shorter durations and overall it's more convenient to get a faster effect instead of building up for weeks.

Because it's not a diet pill that induces appetite suppression upon injection, and when appetite suppression lessens it's a sign of "tolerance"

It's a hormone that plays a central part in energy homeostasis, ie, the weight your body wants to maintain.

The way to envision it is this.

Someone is 250lbs.

You boost your natural GLP level with a .5mg dose of Semaglutide.

Now your homeostasis weight is 240. Since you're above the "set weight", ie homeostasis, the entire biological energy regulatory system, including the complex of effects we refer to as "appetite", physical and psychological, kick in to reduce your weight.

Once you reach the set weight of 240, as determined by how much of the GLP is in your system, appetite suppression stops. If you stay on the same dose, and force yourself to eat more, gaining weight, appetite suppression will return to push you back towards 240.

So to go lower, you increase the dose to .75mg.

Now your homeostasis weight is 230, and appetite suppression returns, until you reach that level.

Once you reach your goal weight, and there's no further appetite suppression, that's the "maintainance dose", at which you maintain the same weight indefinitely.

Because the greater the distance you are from the homeostasis weight set by GLP level and your actual weight, the more intense the effects are, the dose is raised gradually.

 

[benfrankparkway]

How long does reconstituted Tirz last once reconstituted? Per dosing protocol of 2.5mg a week, my 1st vial will last a month... Tried looking up drug info but I got only information for the pens.

 

[Ghoul]

How long does reconstituted Tirz last once reconstituted? Per dosing protocol of 2.5mg a week, my 1st vial will last a month... Tried looking up drug info but I got only information for the pens.

No one can say with certainty.

What's the volume of your 2.5mg dose?

 

[benfrankparkway]

No one can say with certainty.

What's the volume of your 2.5mg dose?

according to what i read on here, and from the drug company .5mL for injection. So my vial is 10mg of Tirz so I reconstituted it with 2mL of BAC.

 

[Ghoul]

according to what i read on here, and from the drug company .5mL for injection. So my vial is 10mg of Tirz so I reconstituted it with 2mL of BAC.

Providing you keep it refrigerated, protected from light and unnecessary movement, use pharma grade BAC, you're doing all you can to maximize its stability.

Under these conditions I wouldn't expect there to be any significant degradation within 4 weeks

 

[unid888]

Because it's not a diet pill that induces appetite suppression upon injection, and when appetite suppression lessens it's a sign of "tolerance"

It's a hormone that plays a central part in energy homeostasis, ie, the weight your body wants to maintain.

The way to envision it is this.

Someone is 250lbs.

You boost your natural GLP level with a .5mg dose of Semaglutide.

Now your homeostasis weight is 240. Since you're above the "set weight", ie homeostasis, the entire biological energy regulatory system, including the complex of effects we refer to as "appetite", physical and psychological, kick in to reduce your weight.

Once you reach the set weight of 240, as determined by how much of the GLP is in your system, appetite suppression stops. If you stay on the same dose, and force yourself to eat more, gaining weight, appetite suppression will return to push you back towards 240.

So to go lower, you increase the dose to .75mg.

Now your homeostasis weight is 230, and appetite suppression returns, until you reach that level.

Once you reach your goal weight, and there's no further appetite suppression, that's the "maintainance dose", at which you maintain the same weight indefinitely.

Because the greater the distance you are from the homeostasis weight set by GLP level and your actual weight, the more intense the effects are, the dose is raised gradually.

Is this a fact based on research papers and by the manufacturer or a theory?

So what happens if you drop 50lbs and get off sema, does your hormone regulating hunger etc. go back to the level it was at 250lbs and now you have to fight to maintain 200lbs with heightened hunger until your hormones balance out after supraphysiological doses that you had from sema??

Or does your 200 lb weight become homeostasis at the same hormone level that you had at 250 lb? I feel like I'm missing some key context here.

Also, what did you think about taking 0.25mg x 3/w to get the effect faster? Is this considered micro dosing or about the same as taking it once weekly?

 

[Ghoul]

Is this a fact based on research papers and by the manufacturer or a theory?

So what happens if you drop 50lbs and get off sema, does your hormone regulating hunger etc. go back to the level it was at 250lbs and now you have to fight to maintain 200lbs with heightened hunger until your hormones balance out after supraphysiological doses that you had from sema??

Or does your 200 lb weight become homeostasis at the same hormone level that you had at 250 lb? I feel like I'm missing some key context here.

Look, I'm not going to expend the effort to explain the nuances underlying the mechanism of action. This is, in effect, how it works.

Maintenance doses are established at the point of weight homeostasis, and a stable weight is achieved, as demonstrated by the long term trials by Novo and Eli to be durable, at those doses, for years. Any idea of tolerance, again, based on the simplistic but admittedly widespread notion of a "diet pill" that loses efficacy over time go out of the window in light of that,

This is how the they're supposed to be used. Indefinitely, like insulin. It's hardly a secret, and found in the prescription directions for clinicians, but for marketing reasons they don't shout "you'll be on this forever".

As to maintaining weight loss without ongoing GLP hormone supplementation, the statistics are dismal. Unsurprisingly similar to statistics that show even after struggling and successfully losing weight via diet and exercise, weight eventually returns to its starting point for the overwhelming majority. Appetite is a potent motivator of behavior, perhaps the most powerfully exerted biological drive after breathing, and in an environment of easy calorie availability, willpower eventually succumbs to food noise. Not dissimilar to other addictions (that also appear to be very successfully reduced with GLP use...).

So yes, appetite returns with a vengeance after stopping GLP use after levels of GLP return to their former state, around 4 weeks.

There is evidence of some degree of metabolic adaptation that occurs as you maintain a lower weight, that appears to make some loss "sticky" after stopping treatment, but that takes a long time.

I guess another analogy is in order here. At what point after Testosterone Replacement Therapy can someone stop and not revert to the low testosterone symptoms they previously had? At what point can a diabetic stop taking insulin, and not revert to glucose dysegulation?

Understanding this is how GLP works should be easy to grasp, it's merely another metabolic hormone, but the deeply ingrained notion that weight is primarily an issue reflective of character, merely an issue of "willpower", to the point most would rather believe that skinny illiterate loser pumping gas is just a better person with more "control" than a product of his biology despite the obvious absurdity.

TLDR, you want to replicate the outcome shown achievable by over 10,000 people in the pharma trials, follow the pharma protocol, titrate up as tolerable until you reach your goal weight, Reduce the dose if appetite suppression continues despite reaching goal weight. Stay at that dose, where you will, essentially, feel nothing, and take comfort knowing a whole host of other life extending benefits are accruing, from reduced systemic inflammation by GLP's interplay with the vagus nerve, to direct action on neurons reducing oxidative damage that will protect your vision against the steady destruction of time.