MESO-Rx
Anabolic Steroids
Giant Semaglutide Thread (and other GLP-1 / GIP agonists)
- Thread starter Doodle
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But that's exactly what I report, the appetite suppression it's not forever unless you keep increasing the dosage but at some point the max dosage is reached and you will get accustomed to it.They weren't designed for any particular effect any more than testosterone is designed for a particular purpose,
GLP and GIP are hormones that play a part in metabolic regulation, released after eating, these drugs are just adding to our natural levels, like TRT for metabolism. Bariatric surgery accomplishes the same thing, since stretching the stomach and intestines (ie, simulating being filled with food) triggers in an increase in the production of those hormones and their receptors.
The impact on appetite isn't a side effect, but part of the system that regulates energy intake. They just targeted diabetes first (already accustomed to daily injections). The big breakthrough was making GLP-1 last a week, like adding long eaters to testosterone,
You eat, nutrients in the intestine trigger GLP release, causing insulin sensitivity to increase so cells are prepped to absorb the incoming energy, blood glucose goes down as cells use it, and appetite is reduced, using the same mechanism that would kick in if you ate a huge meal (gastric slowing, psychological reduction in food appeal, etc) because you don't need more energy. As weight goes down, more GLP is required to suppress appetite since other mechanisms are stimulating appetite to get it back up to whatever your homeostasis level is,
They're not like diet pills that slowly lose effectiveness over time, though I know many people view them that way.
Even most general practioners prescribing these meds don't seem to understand how they work and aren't explaining things properly to their patients (ie, side effects will dissipate and you'll need to take this indefinitely to maintain the weight loss, because it's a chronic condition. Just like you don't stop blood pressure medication once blood pressure has gone down, stop insulin when glucose is controlled, or stop TRT because the man feels better). Apparently many stop taking GLPs after a while, not realizing 95%+ will regain the weight.
If New Obesity Medications Work, Why Do So Many Stop Them?
Recent research suggests that patients prescribed GLP-1s don’t fill their prescriptions or stop taking them. Yoni Freedhoff, MD, discusses the obstacles to patient adherence.www.medscape.com
The advice from experts is that doctors should "sell" the other great health benefits other than weight loss to entice patients to keep taking it, Which is coincidentally my approach as well.
Just the reduction in systemic inflammation alone is worth taking them forever:
My wife couldn't eat shit at 2.5mg now she can easily even so she can't binge anymore, increased at 5mg appetite suppression increased again and now it's fading away all the other benefits are there tho and that's what matters.
She is weighting even a bit more then when she started using a GLP-1 since she is bulking so if it was mathematically like said she should have massive appetite suppression but she hasn't.
Maybe this effect works different for fit ppl using it for different reasons then weight loss..
If we were having immunogenic response and losing effectiveness we would see it in our blood glucose control and other benefits would disappear but they are not.
Probably if you keep pushing yourself to eat the body react and if you are not obese let you push the envelope? I don't know. I'm just reporting first hand how it is for ppl around me that are not the typical GLP-1 users and are more like the one around here
2mg (not even 2.5) gave me COMPLETE control over my cravings/food addictions, which was all I needed to stick to my cut. I didn't experience ANY appetite suppression, even at 2.5mg (well, maybe some...first day it's very hard to eat so I have to space out the first two meals, but then it's all easy).
This type of control is all I ever wanted. In fact, I do not want any appetite suppression...
Musmadar
Member
Your experience makes a lot of sense, and I think a lot of people using GLP-1s for non-traditional reasons (like body recomposition rather than weight loss) are seeing something similar. The appetite suppression definitely fades over time, but that doesn’t mean the drug has stopped working—it just means the body adapts. Like you said, blood glucose control and other metabolic benefits remain, which suggests the mechanism is still active.
I’ve had a similar experience with tirzepatide me and my wife. Initially, the appetite suppression was intense, but over time, I could eat more and more. But even with that, I noticed it helped me build better eating habits—less mindless snacking, better portion control, and a more structured approach to meals. I think that’s the real long-term benefit for people in our situation.
It also makes sense that fit individuals using it for different goals (like cutting or recomposition) will have a different response than someone starting from a place of obesity. The body's energy demands are different, and the hormonal environment isn’t the same. So, while the appetite suppression might not be as extreme forever, the metabolic benefits still make it worthwhile.
Exactly! We don't want the appetite suppression and for example wife she is glad she doesn't have it anymore but I didn't see her do any chest day where she binged like a mofo on sweet stuff for example. She didn't eat two pizzas anymore and only one. She had a lot more control on her cravings, even so she didn't really need it as she is very fit but if she can reap all those other benefits and makes her life easier sticking to a diet... Why not?
Ghoul
Member
Perhaps the problem here is the definition of "appetite".
What exactly, allows you to more easily control your eating habits more easily once "appetite suppression" fades away?
I think what may be happening with short term users is they're conflating the GI effects from slower gastric emptying, which definitely makes it harder to eat, with psychological appetite suppression.
Those GI effects diminish and go away completely once the body adapts to the slower speed of food movement,
But the "psychological" aspect of appetite suppression continues, until you hit whatever weight a dose resets your homeostasis level to, Then you have to increase the dose (which can slow down
gastric emptying again) to get the psychological appetite suppression again. Or if you gain weight at the same dose, those psychological appetite suppression effects return.
Maintenance dose is the dose where you
no longer have the physical side effects, but the psychological aspect of appetite suppression (silencing food noise) continue.
I wonder if those who've never had an issue maintaining a healthy weight, because they have a properly functioning metabolic homeostasis system, primarily experience the temporary physical effects as the "appetite suppression", and that explains the difference in reported experience. The "food noise" psychological part wasn't a problem for them to begin with, so its elimination doesn't make much of a difference.
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Musmadar
Member
First, there’s reduced food thoughts ... even when the intense suppression fades, the constant preoccupation with food just isn’t the same. Cravings feel more manageable, and there’s less of that urge to eat out of habit, boredom, or emotion.
Second, GLP-1s seem to help with improved satiety ... even if I can eat more now than at the beginning, I still get fuller faster and stay satisfied longer. Could be that even the stomach gets smaller in time. This makes it easier to maintain structured eating patterns without feeling like I’m constantly fighting hunger.
Lastly, I think there’s a behavioral component ... after months of eating in a more controlled way, it just becomes second nature. GLP-1s give you time to develop better habits, and once those are in place, it’s easier to maintain them even as the drug’s appetite effects diminish.
So, while the suppression itself may fade, the overall shift in how food is perceived and how the body responds to it remains.
This is exactly my line of thinking, Sampei. I'm eating the same diet I was on when I started my cut, but after Tirz it's all smooth sailing because I just need to eat, sleep, repeat, without worrying about caving in to my cravings which are becoming stronger. I have a tendency to binge eat when I cave in so if I decide "fuck it", that means I'm eating 5-7k calories in one night. Tirz pretty much ELIMINATED this possibility at 2-2.5mg (and it actually seems that it's doing something for my bg, because before it'd be mid-high 70s upon waking, and now it's higher 60s on the same diet -I feel fine- ...).
I never felt this much in control before, this drug is as close to magic as you can get.
Ghoul
Member
Awesome man. It's unfortunate that those who can only tolerate a lower dose otherwise they'll lose too much weight miss out on some of the other benefits, which are mostly dose dependent.
In the future there may be a variant of GLP drugs that minimizes the weight loss / appetite suppression comportment in order to maximize the other benefits like statement inflammation reduction for those who already maintain ideal weight naturally,
The first 2.5mg of Tirz I took yesterday did nothing so far. I know the saturation time is 4 weeks but if the first injection did nothing at all idk how much more I could expect in the next 4 weeks on the same dose.
Could I just go to 5mg next week?
Injected yesterday and both yesterday and today I've been extremely hungry as usual.
Tho I think my digestion might have slowed down a little since usually after coffe in the morning I go to the bathroom immediatly, but today nothing
Could I just go to 5mg next week?
Injected yesterday and both yesterday and today I've been extremely hungry as usual.
Tho I think my digestion might have slowed down a little since usually after coffe in the morning I go to the bathroom immediatly, but today nothing
Juiced_lizard
Member
No do the 2.5mg for 4 weeks then go up to 5mg.
As with anything it takes time to work. Give it time. Some people don’t notice a big difference in “appetite suppression” until 7.5-10mg. Although there are more benefits besides the suppression that’s helping.
Ghoul
Member
If you feel nothing within 3 days I'd say yes, 5mg the following week is fine. If still nothing 7.5mg the following is ok, As soon as you feel an effect however, give it two weeks (doses) before deciding whether to titrate up again. Once effects kick in if you titrate too quickly it can put you in a bad place.
4 weeks for the full effect of any dose, but by two you've got 80% of the effect.
It's not unusual for (mostly) men to feel nothing until 5/7.5/or even, rarely, 10.
That's actually a good thing, better than a strong appetite suppression response at 2.5mg.
Juiced_lizard
Member
You think working up faster is the better approach? I’m just curious.
Faster as in the protocol from pharmaceuticals trials.
thanks, I'll give it another week on 2.5 before deciding if I should up it or ot
anon55
Member
I started at 81kg and I'm currently 59. 1m72. Maybe 7-9% BF now. Amazing drug, changed my life. No more hyperphagia.
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Musmadar
Member
Just make sure you have enough antidiarrheals, antiemetics, and antacids on hand... trust me I know what I'm talking about.
Ghoul
Member
Obviously you know how adamant I am about sticking to the pharma protocol in order to maximize the chances of achieving the success demonstrated in the trials
When you read the in depth prescribing information, there's nothing inherent about sticking to 4 weeks that's clinically significant (other than I note below regarding sides). They're working within the practical limitations of fixed dose 4 pen boxes.
When a patient titrates up, they can immediately go down the following week if it's intolerable (if insurance will pay for a smaller dose box).
There is a safety element ofc since as we know, it takes 4 weekly doses to reach a stable level and fully experience side effects, We also know, that what may feel ".weak" at dose 1, may be too much if that dose is immediately boosted the following week. Dose 2 is really needed to get a sense of the sides that dose will subject to the patient to.
However, when someone feels absolutely nothing at the conventional starting dose of Sema or Tirz, not weak, but NOTHING, in my experience there's no risk titrating up the following week will push one into the "too much". range.
These doses were established to accommodate a wide range of demographics, from the 4' 140lb woman to the 6'5 400lb male.
There's some evidence to suggest the total *proportion* of GLP-1 receptors agonized determines the strength of effect on appetite (and sides).
The larger you are, the more GLP-1 receptors you have.
Males, generally, have a higher density of GLP-1 receptors,
This explains, in part, why females, generally, even at the same body size, typically experience a stronger response at lower doses than males.
So when a guy genuinely feels nothing (not weak, nothing) at the starting doses, experience has shown me that it's safe to titrate up the following week, until something is felt. That's the real "starting point" for that individual's biology. At that point caution is warranted and the usual slow titration should be adhered to.
The prescribing info has "evolved" over time. At one point if you couldn't. reach 2.4mg on Sema within 6 months they advised treatment be stopped, for instance. That was lowered to 1.7mg as the "minimum" within 6 months.
Eventually I think we'll see starting (and max) doses dialed in based on sex and body mass. Maybe even the genetic tests that indicate the density of GLP-1 receptors.
Juiced_lizard
Member
I agree with that being dependent on the individual for sure. I just err on the side of the slow approach I assume. Working up slowly with anything including AASand peptides also. Although I agree there’s probably no problems with moving up except some nausea, GI and other minor disturbances that can be faded away in a few days.
Ghoul
Member
I agree there's no downside to following the 4 week plan, and taking it slow. (also it's fine to stay a a dose level longer if it's still inducing appetite suppression and you're not at goal weight yet).
When it comes to a new user saying they're feeling nothing though, I also know from experience many will get impatient and either quit or do something risky like take another dose before the next week.
In other words, folks will do what they want, so if they're starting to feel impatient enough to mention it, I try to offer a safe path for them to speed things up, rather than wagging my finger at them.
SnowyMiami
Member
The fact that Novo is trying to get 7.2mg semaglutide approved makes me think that loss of effectiveness is becoming a bigger problem. If homeostasis were the whole story, 7.2mg would be starvation/death.
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