longdongsilver
Explorer
In my opinion, this is the correct information
Let’s Talk About Saturation
- Thread starter FLglpguy
- Start date
woundcarping
Explorer
That's a reasonable point — the drop in water weight during those first weeks is the outlier; it's the ongoing 2% reduction that's really on the far end of things.
AngieHolmes
Explorer
For me, this is the approach that does the job. I cut back to half a dose so it stays circulating. That amount keeps bingeing away and keeps food noise from tormenting me, though I have noticed a slow-growing pull toward sweets that I have to watch out for. After a couple-few weeks, I raise it again to my usual 2mg tirz + 2mg reta.
The lower dose feels good to me, and once I go back to my normal dosing (5 days ago, now) I keep feeling good. No sides or glitches. In maintenance I'm planning on 1mg + 1mg, since I know it holds off food noise and regain in my case, but naturally I'll tweak it depending on results.
Anyway, everyone's different; this works for me.
5'8"
SW: 205 Dec '25
CW: 153
GW: 145
Did Sema hit you hard and fast, like a slap to the face, in terms of side effects?woundcarping said:
I experimented with a single vial of Sema (which left 69 on the spreadsheet). It did the job, but the side effects were the harshest I've encountered so far, even though they were fairly mild compared to what most people report and completely manageable in daily life.
Once I reached my first target (200lb) on August 5th and spent some time messing around with trial runs on lower Reta doses, quality of life tweaks, and similar things, I buckled down again to get rid of the remaining ~20lb.
I swapped out .25mg/ week of Sema for 2.5mg of Tirz. Reta went back up to 20mg/week, and Elora sits at 1mg/week. Quality of life so far is pretty much in line with what I had on the reduced dose, and the weight loss trend is running 2 days behind my original 1% week/week projection from 12/12/25.
Bottom line, I'm happy I tried Sema, but I don't plan on adding more personal experience with it.
/
.13mg, then the following day. My whole rationale for using smaller amounts of each was twofold: sidestep possible sides, and get the most out of fat loss plus the extra perks. I was after a bit more appetite suppression. Microdosing sema seemed like the way to get it. And it has delivered.
Nine months into my glp journey, I've stayed quite happy with how things have gone. Not once have I chased a dose big enough to make me gag at the mere idea of food or leave me unable to eat. All I ever wanted was to eat at mealtimes, in a sensible portion, without fixating on any particular food or on how to stack up volume foods for fullness.
woundcarping
Explorer
No, compared to most people it was mild, but on my almost side-effect-free journey it was still “the worst” I’ve dealt with. I started at .25mg, planning to dose it 2x per week. That ended up being too much, so I waited a couple extra days before my next Reta shot to let the Sema fade. I went down to .125mg 2x weekly… a few times I went up to .1875mg but returned to .125mg, 19 shots altogether.
From Sema I got mild malaise and an amplified gag reflex that actually made me throw up; not extreme, but I don’t miss it, and its efficacy is simple to swap out for something with fewer sides, since there are so many options that work.
lessthanhalf
Explorer
This picture shows why tolerance to the weight loss effects of GLP drugs doesn't truly develop. While on a steady tirz dose, the weight line stayed flat for 3 years. If tolerance were developing, that line would climb as time went on.
So receptor saturation could be real, if your dose has the receptors maximally saturated with drug and raising the dose further couldn't produce additional weight loss, but that is the point of diminishing returns and ultimately no added benefit from larger doses, and for most people that point sits above 15mg of tirz, yet this is a distinct matter from tolerance. Whether anyone truly grasps how the incretin receptors operate, I do not know, since they differ greatly from most GPCR receptors, where high doses would bring tolerance, and you certainly cannot use drug doses anywhere close to that level for the vast majority of receptors; with opiates or beta receptors, doses that high would likely be fatal. Even at 12.5 of tirz plus 4 of reta, you would be highly unlikely to have reached the point where larger doses add nothing.
A few months is probably too soon for a genuine stall; usually that takes a bit over a year. Stalling comes from weight loss, where metabolic rate falls because of the weight lost, and it also makes you hungrier so you eat more, and in time you reach a point where the GLP drug no longer creates a calorie deficit, so weight loss stops, though it still keeps you from regaining. When that happens it feels like the drug quit working, but it has not; it is the reason you are not eating twice as much and regaining.
To know for certain what is happening, I would likely need a more precise timeline of the drug doses plus recent weights, along with start weight, target, age, height etc. The stall could simply come from messing with the GLP drugs or from water weight fluctuations.
It sounds like you are now switching to just reta, so you will need to raise the reta dose until it works for you a bit better than 12.5mg of tirz. If you reach 12mg of reta and weight loss halts for a couple of months, then you might need to consider higher doses if there are no side effects or adding in elora.
So receptor saturation could be real, if your dose has the receptors maximally saturated with drug and raising the dose further couldn't produce additional weight loss, but that is the point of diminishing returns and ultimately no added benefit from larger doses, and for most people that point sits above 15mg of tirz, yet this is a distinct matter from tolerance. Whether anyone truly grasps how the incretin receptors operate, I do not know, since they differ greatly from most GPCR receptors, where high doses would bring tolerance, and you certainly cannot use drug doses anywhere close to that level for the vast majority of receptors; with opiates or beta receptors, doses that high would likely be fatal. Even at 12.5 of tirz plus 4 of reta, you would be highly unlikely to have reached the point where larger doses add nothing.
A few months is probably too soon for a genuine stall; usually that takes a bit over a year. Stalling comes from weight loss, where metabolic rate falls because of the weight lost, and it also makes you hungrier so you eat more, and in time you reach a point where the GLP drug no longer creates a calorie deficit, so weight loss stops, though it still keeps you from regaining. When that happens it feels like the drug quit working, but it has not; it is the reason you are not eating twice as much and regaining.
To know for certain what is happening, I would likely need a more precise timeline of the drug doses plus recent weights, along with start weight, target, age, height etc. The stall could simply come from messing with the GLP drugs or from water weight fluctuations.
It sounds like you are now switching to just reta, so you will need to raise the reta dose until it works for you a bit better than 12.5mg of tirz. If you reach 12mg of reta and weight loss halts for a couple of months, then you might need to consider higher doses if there are no side effects or adding in elora.
At least it's reassuring that, worst case, I could grab a kit and run it alongside what I'm already taking (perhaps .13 mg per week?). Right now I'm on 6 mg of Tirz, having stepped down from 9mg, and this dose feels just right for me.
Thanks!
This is something I constantly need to remind myself about. That number on the scale can be deceiving. And other times, despite having eaten, being properly hydrated, and feeling fine, you just can't push through that final set at the gym.
It comes across as a personal shortcoming, but that's not what it is. Simply showing up and doing the work already counts as a victory!
Nerker
Explorer
I’ve been turning this concept over in my head. I grabbed a few white papers and ran them through AI to simplify the language. I put this together to organize my thoughts: I’m not claiming every bit of it is correct. Still, the “muscle to fat” angle holds up.
GLP 1 receptors are able to “go inside” the cell and then emerge prepared to receive again. Think of it as a revolving door of receptors. This gets around desensitization. Glucagon receptors also “recycle” themselves, though the intracellular process is more involved. GIP receptors become numb. Think of that as a factory shutdown. This supports the GIP focus. (It prevents fat cells from storing energy). Once the med wears off (trough), the factory comes back online.
“Therapeutic Resistance” --see below
The explanation for why we don’t cycle our GLP drugs is that after Round 1 the fat to muscle ratio has shifted. When we quit, we “gain the weight back” as fat. But during the first round we lost some muscle. So on restart, the body defends the muscle you still have. B/C there’s less muscle, the hypothalamus puts the brakes on your metabolism. Fat burning therefore halts, and it feels like the drug isn’t hitting the way it did on R1.
If you did resistance work and managed to gain during R1, you also have muscles burning calories through their activity. So your “engine” is different from when R1 began. Insulin can sink into the new muscle.
My plan is to pause for 6 months to try new toys. Then start again to cut. The challenge will be staying disciplined in a high protein / low carb environment with resistance work, trying not to alter the “muscle to fat” ratio. Think of this as protecting the engine. When I restart, the low dose ramp up might “check” and find the current ratio is “good” (ie. adequate muscle is seen and pumping the metabolism brakes does not occur. )
GLP 1 receptors are able to “go inside” the cell and then emerge prepared to receive again. Think of it as a revolving door of receptors. This gets around desensitization. Glucagon receptors also “recycle” themselves, though the intracellular process is more involved. GIP receptors become numb. Think of that as a factory shutdown. This supports the GIP focus. (It prevents fat cells from storing energy). Once the med wears off (trough), the factory comes back online.
“Therapeutic Resistance” --see below
The explanation for why we don’t cycle our GLP drugs is that after Round 1 the fat to muscle ratio has shifted. When we quit, we “gain the weight back” as fat. But during the first round we lost some muscle. So on restart, the body defends the muscle you still have. B/C there’s less muscle, the hypothalamus puts the brakes on your metabolism. Fat burning therefore halts, and it feels like the drug isn’t hitting the way it did on R1.
If you did resistance work and managed to gain during R1, you also have muscles burning calories through their activity. So your “engine” is different from when R1 began. Insulin can sink into the new muscle.
My plan is to pause for 6 months to try new toys. Then start again to cut. The challenge will be staying disciplined in a high protein / low carb environment with resistance work, trying not to alter the “muscle to fat” ratio. Think of this as protecting the engine. When I restart, the low dose ramp up might “check” and find the current ratio is “good” (ie. adequate muscle is seen and pumping the metabolism brakes does not occur. )
monkymate
Explorer
This
Sema didn’t cost much, and only a small amount was needed to keep hunger in check, which let me remain on a 3mg/3day cycle of Reta. I take the Sema once a week at .5 mg. I also have Tirz and Cg on hand, though I haven’t touched either of them.
monkymate
Explorer
Maybe I'm just lucky. Other than shedding pounds quickly, I haven't dealt with any significant side effects—and still haven't. My wife, though, got hit with every single one of them. I began at .25, stayed there for 4 weeks, then bumped up to .5 once the food noise came creeping back. My Reta dose stayed unchanged.