MESO-Rx
Anabolic Steroids
Giant Semaglutide Thread (and other GLP-1 / GIP agonists)
- Thread starter Doodle
- Start date
RAW95
Member
Exactly that — I'm waiting on my second dose to feel the suppression effect more strongly.
To tell you the truth, right now everything feels perfect.
Could I eat more if I wanted to? Yes.
But the craving just isn't there.
That's the plan. If the suppression is still there by the end of my fourth week, I'll stick to the same dose and only titrate up when I feel it's necessary.
Ghoul
Member
And conversely if suppression drops off feel free to titrate up earlier. My only rule of thumb is to give each dose 2 weeks. There are times where a particular dose seems manageable or weak in the first week, and in a rush to lose weight more quickly someone will titrate up the following week and get slammed.
Still running Tirz at 10mg - decided not to increase the dose since it’s working like a charm. Just did some bloodwork to check how things are going while on cycle + 4iu of HGH daily:
Glucose – 81
Hemoglobin A1c – 4.9
Insulin – 8.1
Everything’s smooth, feeling great. No plans to hop on Reta for now!
Glucose – 81
Hemoglobin A1c – 4.9
Insulin – 8.1
Everything’s smooth, feeling great. No plans to hop on Reta for now!
RAW95
Member
If the suppression persists after a full week, do you think it would be wise to postpone the shot by 1–2 days?
I have my second 2.5mg dose scheduled for tomorrow, but the suppression is still strong. If it doesn't start to wear off by then, I’d prefer not to intensify the effect further
CubanQuentin
Member
I'm 99% sure I know the answer but I'll ask just to be sure...
Semaglutide injection should be subcutaneous, right?
Semaglutide injection should be subcutaneous, right?
If Ghoul is still around I'd like to ask him for advice. If one was, supposedly, developing some kind of immunity to tirzepatide, what can be done?
I started tirz 4 months ago, got to 5mg and it killed my appetite and lost a lot of weight very fast, to the point I had family members ask me it I was ok, so I decided to keep at 5mg. overtime tho it started to loose effectivness, my appetite kept increase and I started regaining weight. So now it got to a point where I'm barely even feeling it anymore and I regained fat. I wanted to up the dose but didn't have enough tirz on hand, ordered more 4 weeks ago but it's taking forever to arrive. What do I do now? I'll up the dose once more tirz arrives but I'm afraid I'll keep building an immunity to it. I always did 1 injection per week diluted to 1ml per injection.
I never missed injections (just one time I delayed it by one day).
Last year I had done 3 doses of ozempic 0.25 but felt horrinle and stopped, don't know if it could have affected things
I started tirz 4 months ago, got to 5mg and it killed my appetite and lost a lot of weight very fast, to the point I had family members ask me it I was ok, so I decided to keep at 5mg. overtime tho it started to loose effectivness, my appetite kept increase and I started regaining weight. So now it got to a point where I'm barely even feeling it anymore and I regained fat. I wanted to up the dose but didn't have enough tirz on hand, ordered more 4 weeks ago but it's taking forever to arrive. What do I do now? I'll up the dose once more tirz arrives but I'm afraid I'll keep building an immunity to it. I always did 1 injection per week diluted to 1ml per injection.
I never missed injections (just one time I delayed it by one day).
Last year I had done 3 doses of ozempic 0.25 but felt horrinle and stopped, don't know if it could have affected things
Last edited:
CubanQuentin
Member
From what I've read, it's more likely that your appetite suppresion has tapered off due to you losing so much weight, rather than building a resistance to the drug. In which case your best course should be to up the dose. If you can't do it yet wait until your next batch of tirz arrives
If you are gonna up the dose you probably want to start using 2ml of BAC water instead of 1 in order to not have a solution with too much concentration of tirz, which again from what I've seen tends to aggravate side effects in some users
The bad reaction to semaglutide (ozempic) most likely means nothing in regards to this
Ghoul
Member
What you're describing sounds like, and is more likely to be the normal course to expect with GLP, which is widely misunderstood by people who think they work like a diet pill. IE, x dose=a certain amount of appetite suppression, and if it lessens, that indicates a problem or tolerance.
This analogy may help clear things up.
At a given dose of any GLP, your body's weight "thermostat", the homeostasis weight it wants to maintain, is set at a certain point. This varies significantly between individuals.
I'll use some arbitrary numbers.
Let's say you're 250lbs.
A 5mg dose sets your "thermostat" at 240lbs.
Above 240lbs, at 5mg, you'll experience appetite suppression, and the other sides associated with GLPs.
As you approach 240lbs, the effect will weaken, and once you hit that weight you'll feel nothing because you've reached homeostasis, the weight your system wants to maintain. There will be a little variation around that target, but if weight increases by more than a few pounds, using the same 5mg, appetite suppression and the other effects will return to push you back towards 240lbs.
To go lower you increase the dose, say, to 7.5mg, which now sets the "thermostat" to 230lbs and the same process happens until you reach that level.
Once someone reaches goal weight, you stop increasing the dose. or even drop it slightly. This becomes the "maintenance" dose where there's no appetite suppression, no sides, unless you force yourself to eat beyond your hunger or make some other change that causes a weight gain, then the effects return to push you back down.
The long term. 3-4 year studies show those on maintenance doses stay at their goal weight, drop a little more or go up, usually within 5lbs either way for years on the same dose,
These compounds mimic natural hormones, so the effect doesn't "wear off" over time any more than long term TRT would cause a loss of sensitivity to testosterone.
However, with UGL there's a big question mark because they're simply not made to the same standard as pharma, and could induce immunogenicity that could cause a progressive weakening of effect.
The indicator of that would be at a given dose, appetite suppression never returns even as your weight progressively increases.
How much weight have you gained back vs how much was initially lost on 5mg?
I had initially lost 25lbs on 5mg, it got me to my goal so I planned to maintain from there. then appetite started increasing rapidly and I gained back anout half of that, this is why I was worried about immunity buildup.
Tho I also wonder if this regain is a sort of "rebound" because the initial weightloss was very fast, I had lost those 25lbs in just 4-5weeks because my appetite was non existant
Ghoul
Member
It could be any number of things because it's UGL. The batch might be degrading for one reason or another. Vial to vial inconsistencies.
Since you have a fresh batch coming, see how it goes with that. If 7.5mg doesn't bring you lower than 5mg did initially, and the same thing happens, appetite starts returning and you lose that much ground again (50% weight regain), you probably are developing some immunogenicity and should consider switching to Reta or Sema, or going to pharma if you can.
Even with pharma protein therapeutics, some minority of patients often develop immunogenicity (because of individual variation in immune response).
Let me mention, regarding immunogenicity what we're talking about here is the immune system clearing the drug from your system(seeing it as an invader), reducing its effectiveness.
It's measured by checking levels of antibodies that form against the protein drug. Unfortunately, these tests are developed for and only carried out in clinical trials (except rHGH antibodies which can be tested for in regular blood labs).
The way it's dealt with is:
1. Increasing the dose.
In some, immunogenicity increases to a fixed level, and can be overcome with a higher dose without further immunogenicity developing.
Counterintuitively, larger doses can convince the immune system that it's not an invader, and "normalize" its presence, reducing immunogenicity, and it's only small doses that cause a problem.
2. Switching brands.
This is how it's handled with rHGH when signs of a loss of effectiveness appear (especially in children and the expected growth stops) The different contaminant profiles between pharma brands may mean one may not trigger the same drug neutralizing effect of another.
3. Taking a drug "holiday".
This can lower immunogenicity, and restore effectiveness. But no one can say how long with GLPs because it hasn't been studied. While immunogenicity does develop in some people on pharma GLPs, with Sema and Tirz it's always a low level, levels off over time, and usually drop a bit. So those people respond a little weaker to the drug, but they still work. But that's the ultra clean pharma compound, not UGL, which could induce progressively worsening immunogenicity with every dose.
It's worth noting some earlier GLPs did cause progressively increasing immunogenicity and loss of effectiveness in some users. Those diabetics lost control over glucose within a year or so and as a result were switched to another GLP or back to insulin.
Loss of therapeutic effectiveness can definitely happen with any protein drug. It's a major difference between peptide/proteins and "regular" small-molecule drugs which almost never cause interactions with the immune system.
I forgot to mention, if you aren't filtering, you should. Most of the contaminants that trigger and worsen immunogenicity can be removed by filtering.
Large protein aggregates, and things like glass or rubber particulates. The latter two impact immunogenicity because they get the immune system's attention, when it might otherwise not be triggered. Once on the scene of the injection, they "learn" the epitope pattern of the peptide/protein, and use that information to clear it out more quickly in the future. This is called the adjuvant effect, and vaccines use this to their advantage.
"Spike" vaccines literally have spikes attached to disease proteins that secure them to contaminants that draw the immune systems attention so they learn the proteins are invaders. Otherwise, the proteins themselves may not draw the immune systems attention, and immunity isn't developed (an example of when triggering maximum immunogenicity is actually desirable).
Last edited:
thank you. I have some filters on the way because I was going to make some carnitine, will filter the tirz from now on.
Amd if I eventually get up to 15-20mg and I still get this loss of effectivness I'll try switching to reta or sema
Ghoul
Member
Like I said though, don't panic and think a return of appetite is a problem. It most likely isn't. I've been on a maintenance dose of Tirz for years, and feel nothing at all. I get hungry, eat, stop eating when satiated, and get no sides whatsoever. My weight's stayed within the same small "swing range" for a long time.
If you introduce other drugs, or make a significant change to your workout routine that impacts metabolism, you may find appetite being suppressed by those and have to lower the dose to avoid losing too much weight.
I optimized thyroid levels the "ideal" 20th percentile range for my age, and dropped 10 more pounds in a few weeks, with the same calorie intake, so had to lower the Tirz dose to regain the appetite needed to put it back on.
Have you considered experimenting with reta? People seem to love it.
Ghoul
Member
I'm fortunate enough to have access to pharma Tirz (though I've used UGL).
Since it works and it's pharma, I don't see enough of a benefit to warrant switching to UGL Reta. Reversal of (common but rarely diagnosed) non-alcoholic fatty liver disease was the reason I went from Sema to Tirz, and Reta does that even faster. But at this point I think my liver is as healed as it's going to get.
Reta seems easier to dial in a dose for those who don't want appetite suppression but still get the insulin sensitivity, inflammation reduction, blood vessel, nerve, liver, and heart benefits of GLP/GIP agonism.
I'm more interested in the GLPs under development that are combined with growth hormone boosting compounds.
Supposedly the appetite reduction is qualitatively different to tirz. Works more on satiety than being an off switch to appetite, which helps people be able to eat healthy foods and enjoy them more.
The preliminary results in trials are showing improvements over tirz in kidney function parameters and greater reduction in lipids compared to tirz.
I haven’t tried myself because I wasn’t sure I wanted to increase my resting heart rate, and the non fda approved nature made me hesitant. However I may still try it in the future.
It’s good that you have pharma tirz available. In the UK you can actually buy Mounjaro from the pharmacy if you have a bmi over 30. And it’s roughly £170 pounds for 5 doses of 15mg once they let you titrate to that dose.
However I am not obese so I can’t really obtain that without some kind of fraud that I don’t feel like doing.
The SSA tirz works just fine, with lasting suppression. It’s less noticeable complete disinterest in food that you get when first starting but I think that’s normal for even pharma stuff.
I filter it to 0.1micron. So I feel this is a reasonable risk to reward ratio.
It’s interesting, if they add IGF-1 agonism, will that impact ones own production of growth hormone etc. I’ve only seen that one small molecule (bioglutide) claim to target IGF-1 just yet. We’ll have to see whether they get anywhere with it.
Ghoul
Member
The data looks good but is a little thin compared to Sema/Tirz.
There's an increasing focus on separating the expected improvement in metabolic markers from weight loss, from improvements coming from other, direct mechanisms*. Since Reta induces faster weight loss, and all the metabolic markers are a "snapshot in time". it's hard to say what reta does better that isn't explained by the impact of faster weight loss.
That's said, Reta pulls glucose from the liver and dumps it into the blood which appears to offset the fatigue that's common at the beginning of Sema and Tirz treatment. That's only temporary with those, but Reta avoids it so it may be a "gentler ride" for new users.
*there's a ton of evidence supporting the existence of direct benefits independent of weight loss via the GLP receptors present in a vast number of tissues from neurons to heart muscle, but so far studies on non-diabetics / non-obese people are virtually non-existent because of a lack of clinical justification. The ongoing GLP studies on drug addicts will probably give us the best insight so far on the impact to health in physically "healthy" people.
thanks for always responding to everyone's questions. I'll keep everything as is, go up with the tirz and I'll add some carnitine since I doubt that will have a negative impact (doing it more to have more energy rather than more fat loss). If I'll be able to afford it I'll switch to pharma in the future
OldGHGuy
Member
I read somewhere that 1 out 4 people in the US have fatty liver disease. I also saw studies that Anavar can actually cause it and/or make it worse, as can all orals I suppose. Curious to hear about your experience with it and how Tirz helped
Ghoul
Member
GLPs completely reversed Stage 1 NAFLD to no fibrosis and no detectable liver fat on MRI.
I had no symptoms and discovered the NAFLD while having a routine abdominal sonogram.
Rate's been climbing every year with about 40% of adult males now having Non-alcoholic fatty liver disease. Untreated it turns cirrhotic, which is irreversible.
Similar threads
- Question
