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?

 

[Sampei]

Remember it only feels like an appetite suppressant until you hit the weight homeostasis for that dose.

It's not a diet pill that reduces appetite regardless of weight.

If the room temperature (weight) and the thermostat (glp) are matched, nothing is happening. That's what a maintainance dose is. You feel normal. There's no appetite suppression. Drop more weight and appetite fires up to bring weight back up. Gain weight, and appetite suppression returns.

GLPs turn the thermostat down.

This is the mechanism of action people can't seem to grasp. It's not even specific to the drug, it's the body's natural weight regulation system.

But in the absence of this knowledge, that the body seeks to maintain energy homeostasis, and weight issues, underweight and overweight are usually attributable to a malfunction in this system, it's a paradigm shift in thinking that's going to be difficult to grasp.

Yeah but so they can't be used for a bodybuilder as you want to increase the weight and if when you do it suppress your appetite you are fucked : /


Btw I'm not sure you are right here @Ghoul because for example, on sema I was gaining weight at 1mg and my appetite suppression was non existent when instead at first it was very strong but on both instant I kept my same weight. So the appetite suppression just became less and less with time without my weight changing, surely not decreasing.

If it was like you are saying I should have got a stronger appetite suppression when I tried to bulk on it instead nothing happened except I had excellent BG control.

 

[Ghoul]

Yeah but so they can't be used for a bodybuilder as you want to increase the weight and if when you do it suppress your appetite you are fucked : /


Btw I'm not sure you are right here @Ghoul because for example, on sema I was gaining weight at 1mg and my appetite suppression was non existent when instead at first it was very strong but on both instant I kept my same weight. So the appetite suppression just became less and less with time without my weight changing, surely not decreasing.

If it was like you are saying I should have got a stronger appetite suppression when I tried to bulk on it instead nothing happened except I had excellent BG control.

Insulin is a shit business the pharma companies are trying to escape. I'm sure there are insulin sensitivity increasing meds in development for all the normal BMI diabetics who cannot use GLPs because they can't afford to lose weight. It's still going to be a big moneymaker even though it's not weight loss related...hopefully soon for you bud. I don't really follow diabetic pharma pipeline so I don't know what's going on in that area.

Maybe a more "selective" glp peptide will be the answer.

 

[OilCarrier]

"I am a walking glp-1 encyclopedia"

Lol, thanks immensely for your continued input here and in other threads.

Things i now worry about since last time we spoke:

- Is there a risk for pancreatic cancers with GLPs?

- In follow up of these drugs creating antibodies if using incorrect dilution rates and or dosage protocols, or start/stopping protocols, is there increased risk for autoimmune responses suppressing our natural or unnatural hormone functioning? GH as an example, but other hormones maybe as well?

- If so, how can one be comfortable using these, when it might destroy other processes in our bodies?

 

[Ghoul]

Lol, thanks immensely for your continued input here and in other threads.

Things i now worry about since last time we spoke:

- Is there a risk for pancreatic cancers with GLPs?

No. There is no evidence of increased cancer from any GLP class drug. Even the thyroid cancer risk "black box warning" on boxes of Wegovy and Ozempic in the US (but not Europe) has been acknowledged to have been a mistake. To the contrary, all-type cancer risks are lower with long term use. In large part due to lowered systemic inflammation.

- In follow up of these drugs creating antibodies if using incorrect dilution rates and or dosage protocols, or start/stopping protocols, is there increased risk for autoimmune responses suppressing our natural or unnatural hormone functioning? GH as an example, but other hormones maybe as well?

- If so, how can one be comfortable using these, when it might destroy other processes in our bodies?

The FDA has been increasingly vigilant to the threat of immunogenicity from Peptide/protein drugs. It's what drove them to ban a number of popular peptides from being dispensed by licensed compounding pharmacies last year. Ipamorelin, for instance, a growth hormone secretagogue, was singled out for not being studied for the potential cross-immunity to natural Growth Hormone Releasing Hormone. This risk is even greater since the peptide itself isn't produced under FDA supervision, making it more likely to suffer from problems like aggregation, a known immune system trigger.

https://www.fda.gov/media/182088/download

Luckily, Tirz and Sema have been extensively studied and FDA approved for its immunogenicity potential. However, this is under specific pharma conditions, ie, dilution rate, dosage, frequency of administration, formulation, and even the container (the pen). If any of those parameters change, a new immunogenicity study must be conducted and approved by the FDA.

We can't control the formulation of UGL but we can follow the rest to minimize risk. In addition, GLPs haven't been shown to be the worst immunogenic inducers as a group. Some are much worse in this regard, like Tesamorelin. Already known to produce significant immune reponse in its original 1.5ml dose formulation, the pharma company reworked it to concentrate the dilution by 4x to reduce injection volume. A new immunogenicity study was required, and as expected it got worse, creating a stronger immune response, but was still acceptable when used as prescribed.

The FDA rejected the latest proposal to release an 8x concentrated formula, expressing great concerns about pushing immunogenicity potential even further. In other words, 8x might barely be acceptable in a pharma study, passing FDA requirements, but what if the end user leaves it out for an hour at room temperature, or accidentally take a second dose in the same week? The margin for error was too small and FDA demanded much more extensive study before they'll approve it.

FDA Denies Approval of F8 Formulation of Tesamorelin for HIV-Related Lipodystrophy

Tesamorelin is a growth hormone-releasing factor analog that is used to treat excess abdominal fat in adults with HIV who have lipodystrophy.

www.empr.com

And yet, with the vast majority of peptide users randomly making their own "8x concentrations" of various peptides, there's no telling what long term harms they're inflicting by making themselves guinea pigs.

We see "signals" of this all the time here. "My HCG stopped working", or someone claims they've suddenly gotten "bunk" from a peptide supplier, when the batch tested fine and it had been working previously.

So the answer is. if you stick to what's already been validated as safe, despite the possibility our UGL product has some fucked up immunogenicity inducing element we're unaware of, the risks are minimized if you control what you can, and replicate the pharma protocol as closely as possible.

Then you need to also balance the undoubtedly positive benefits for health using these drugs offers against the risk. If you exercise reasonable care, I think the reward far outweighs the small risk in this case. If you're reckless, as too many are with GLPs (and all peptides tbh) I think, the aftermath of your case may make for an interesting case study in some medical science journal in a decade or two.

 

[Fat]

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...

pubmed.ncbi.nlm.nih.gov

Imma skip the others for now unless anyone cares. Much of this data is non-specific and proprietary.

Thanks, now we know the nanomolars how can we find out how much glp1 there is in 2.5mg tirz and what is the dose equivalent on semaglutide?

I heard 2.5mg Tirz is equivalent to 0.5mg Semaglutide

Can someone confirm this?

 

[Fat]

Also respected and well know member Type-IIx said

GIP functions in fat cells to increase fat accrual. [1].

From [1]: "In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-stimulated incorporation of fatty acids intotriglycerides, (3) increase insulin receptor number, and (4) increase sensitivity of insulin-stimulated glucose transport."

"With that in mind, the following hypothesis may be proposed: individuals with a condition of increased GIP responsiveness may be more prone to obesity and hyperinsulinemia. Increased GIP responsiveness may manifest itself in the form of either increased affinity for GIP by GIP receptors, increased GIP receptor number, or increased synthesis and secretion of GIP following normal meal stimulation. The increased GIP responsiveness would likely increase insulin release resulting in greater and prolonged hyperinsulinemia. To compound this abnormality, GIP can also increase the affinity of the insulin receptor for insulin as well as increase the insulin-like effects in fat cells, all of which may serve to increase efftciency in the accumulation of triglycerides in fat cells. Thus, anecdotal accounts of individuals accumulating fat tissue mass at greater rates under normal meal conditions maybe a consequence of increased GIP responsiveness. Such individuals have greater efficiency in fat storage as a result of increased GIP and insulin responses when compared with normal persons." [1].

So why are people here saying GIP stimulates lipolysis? Who is correct?

Should we be concerned that tirz increase fat accrual if that is true?

 

[Ghoul]

Also respected and well know member Type-IIx said

GIP functions in fat cells to increase fat accrual. [1].



So why are people here saying GIP stimulates lipolysis? Who is correct?

Paradoxically, it does both. I'm going to use somewhat imprecise analogies to try and make this understandable.

Like GLP, GIP is released in response to food intake. It preps fat for energy storage, by increasing blood flow and other mechanisms. The same process that allows fat to more easily store excess energy also eases the path for lipolysis (releasing stored energy) in a calorie deficit.

Considering GIP is naturally secreted when taking IN food, storage from the presence of excess calories would be far more likely than release through lipolysis.

Basically it "opens the door" of fat cells through which energy can enter OR exit.

Here's the magic. GIP also induces satiation through a direct effect in the brain. "Ahhh, we've eaten enough" it whispers to the hypothalamus.

But with Tirz, this is all happening in the absence of food intake, you feel satiated, the "door" of fat cells are opened and you get some of your energy requirement satisfied from lipolysis (fat loss).

 

[egruberman]

Thanks, now we know the nanomolars how can we find out how much glp1 there is in 2.5mg tirz and what is the dose equivalent on semaglutide?

The binding affinity to the GLP1 receptor is only one aspect of the pharmacokinetics and isn't directly translatable. There is clinical data that give us a better handle on dose equivalency.

 

[Fat]

Paradoxically, it does both. I'm going to use somewhat imprecise analogies to try and make this understandable.

Like GLP, GIP is released in response to food intake. It preps fat for energy storage, by increasing blood flow and other mechanisms. The same process that allows fat to more easily store excess energy also eases the path for lipolysis (releasing stored energy) in a calorie deficit.

Considering GIP is naturally secreted when taking IN food, storage from the presence of excess calories would be far more likely than release through lipolysis.

Basically it "opens the door" of fat cells through which energy can enter OR exit.

Here's the magic. GIP also induces satiation through a direct effect in the brain. "Ahhh, we've eaten enough" it whispers to the hypothalamus.

But with Tirz, this is all happening in the absence of food intake, you feel satiated, the "door" of fat cells are opened and you get some of your energy requirement satisfied from lipolysis (fat loss).

View attachment 299277

Thank you for explaining.

Do you think bodybuilders should be concerned with using tirz for bulking?

Surely you wouldn't want to use this in an energy surplus then

I know Type-IIx suggests we use Semaglutide

 

[Ghoul]

Thank you for explaining.

Do you think bodybuilders should be concerned with using tirz for bulking?

Surely you wouldn't want to use this in an energy surplus then

I know Type-IIx suggests we use Semaglutide

That's a really interesting question. Is the fat storage enhancing effect meaningful when taken in a low enough dose to allow for bulking?

I often think we need another million researchers or several centuries to answer all the questions raised by these compounds being used by ever more diverse populations, especially those without a metabolic disorder.

Here's what I know, based on work done in 2024 regarding body composition and Tirz.

In a small group of diabetics in this study, in a normal Tirz dose induced calorie deficit, abdominal visceral fat was significantly reduced, liver fat was significantly reduced. Abdominal subcutaneous fat increased, but to a much smaller degree than abdominal visceral fat decreased. This is a healthy recomposition of fat.

My suspicion, but just a guess I'll admit, is that if the dose of Tirz is so low you can effectively bulk, with regular workouts, the threat of accelerating fat gain would be minimal or even offset by other metabolic impacts of GIP, like increasing glucose transport into muscle, making workouts easier and keeping it from contributing to fat accumulation.

 

[Fat]

In a small group of diabetics in this study, in a normal Tirz dose induced calorie deficit, abdominal visceral fat was significantly reduced, liver fat was significantly reduced. Abdominal subcutaneous fat increased, but to a much smaller degree than abdominal visceral fat decreased. This is a healthy recomposition of fat.

Was these diabetics training and eating enough protein? gaining fat isn't uncommon for those crash dieting/ consuming low calories as you are losing lean body mass so end up in a skinny fat position

Thanks

 

[Ghoul]

Was these diabetics training and eating enough protein? gaining fat isn't uncommon for those crash dieting/ consuming low calories as you are losing lean body mass so end up in a skinny fat position

Thanks

Diet and exercise were not controlled for, so probobly not. We have to remind ourselves that in many aspects, we're still in the infancy of these treatments.

I will add however, it's not unheard of for some patients, using the pharma protocol, to experience no weight loss until reaching Tirz doses of 7.5mg+. Meaning they've been on it for 3 or 4 months, mostly in a state of calorie surplus (and then a calorie neutral state, before finally getting sufficient appetite suppression and a calorie deficit.).

I have never come across a report of someone in their first few months, using an "ineffective for appetite suppression" dose say "I think I'm putting on a lot of fat!".

That may not mean much, but since ANY negative experience on GLPs is total click bait and widely reported, usually not in context and blown out of all proportion, ie, "OMG gastroparisis" I would think we would've heard something by now if fat gain was turbocharged at these low doses. Some of the millions of patients are being obsessively measured by themselves or clinicians, so I would've expected some signal out there, yet there's been none.

 

[egruberman]

Do you think bodybuilders should be concerned with using tirz for bulking?

Anecdotally, it’s worked for me. I’m more concerned with staying relatively lean than gaining absolute mass. I’m up about 15lbs in ~8 weeks and I appear to have gained very little to no fat.

 

[Fat]

Anecdotally, it’s worked for me. I’m more concerned with staying relatively lean than gaining absolute mass. I’m up about 15lbs in ~8 weeks and I appear to have gained very little to no fat.

Are you on GH or more than TRT dosages?

Anecdotally, I've seen on reddit that most people can maintain their weight with these drugs even when they're trying to overeat and if I am not mistaken the research says those that use tirz lose less lean body mass than semaglutide so the lipolysis does make sense.