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

Okay, thanks for the reply. Well, I will try another 3mg for a week and if I don't see any effect, I will switch to Tirz.

Does it make sense to take a break?

As Sampei notes, not only will it not help, it could cause a permanent reduction of effectiveness once you go back on.

When considering Tirz, keep in mind you'll need to start at 7.5mg, and may need as much as 10mg before feeling an effect. So in other words, assume you'll end up on a 15mg dose (or possibly higher) to reach greater weight loss. Just so you can calculate how much you'll need, costs etc. Luckiky Tirz can be found very inexpensively, though not the bargain Sema is.

It will provide additional health benefits though, so that's a plus.
 
Anyone else experienced troath pain with tirz? as soon as i injected my troath started hurting a little. it's been about 5hours and it still hurts(it's just a minor pain but never heard of this) not swollen and I can breathe and eat fine
 
Anyone else experienced troath pain with tirz? as soon as i injected my troath started hurting a little. it's been about 5hours and it still hurts(it's just a minor pain but never heard of this) not swollen and I can breathe and eat fine

Like sore? Acid reflux is common. But is this your first dose? That's really fast if it is.
 
Like sore? Acid reflux is common. But is this your first dose? That's really fast if it is.
second. last week 2.5 noticed slower digestion but nothing else. did 5mg today, immediatly noticed I felt fuller after eating a much smaller lunch than usual but got a sore throat, no acid reflux, no nausea.
 
second. last week 2.5 noticed slower digestion but nothing else. did 5mg today, immediatly noticed I felt fuller after eating a much smaller lunch than usual but got a sore throat, no acid reflux, no nausea.

It can be difficult to connect a sore throat to acid reflux. Some people get misdiagnosed as to the cause of a chronically sore throat for a year or more since it can happen in the absence of other acid reflux symptoms.

Obviously it could be anything, but if it's connected to the GLP, it's acid reflux from slowed gastric emptying causing a backup.

Stomach acid is also weakened with GLPs, so even if you've had "heartburn" before, it may be weak enough acid that you don't feel it in your esophagus, but you do in the more sensitive throat area.

It'll probably ease off after a little while as you adjust.

Gastric emptying slows faster than the additional appetite suppression kicks in when increasing the dose, so many times people will eat more than they can handle during this transition period of a couple days, inducing more side effects.
 
This thread made me learn a ton and helped me greatly so i hope you guys dont mind if i pick the brain from the collective here and be frank.

In my Family NAFD (Non-Alcoholic Fatty Liver disease) is a big thing.
And i want to try and help them whenever its through supplements or being able to directly speak to their doctor and prevent me from getting it in a severe way despite it being more of a genetic thing.

They all have:

Shitty Insulin Sensitivity (HOMA above 5.0)
Elevated Hba1c (5.0 and higher)
High Cholesterol
High Triglycerides
Really low SHBG
High Liver markers (GOT above 50, GPT above 100, GG above 100)

Luckily, for me its just an elevated GPT, slightly higher cholesterol and shit insulin sensitivity which already is improving a lot due to my current cut and will continue to do so.

Upon talking to my Doctor, he wants to put me right away on

Atozet (10MG Ezemtib/10mg Rosuvastin)
Metformin (1000mg 3x a day)
25mg Jardiance (1x daily, taken in the morning)

And since studies regarding GLP1 seem to be really promising (thanks @Ghoul for providing so much Information here) i am planning on jumping on Tirz as well.

Would appreciate any experience, supplement recommendations, medications and so on!
 
Would appreciate any experience, supplement recommendations, medications and so on!
o o
I'm not very knowledgable on the matter but I would think that any anti-oxidant/ anti inflammatory molecule would help liver funcion.
NAD+ & NAC are great, Glutathion is great, Melatonin (in high doses) is probably the most powerful anti-oxidant, make sure to have a adequate amount of B vitamins, if not supplement them (just be carefull with B3 and B6 toxicity risk, look up how much is safe to take). Even if you meet the recommended daily intake of these you could see some benefit going higher.
Also try TUDCA (Tauroursidexycholic Acid) for liver support.
Red Rive Yeast also works to lower cholesterol, kinda like statins
When it comes to GLPs I think someone on here showed a graph of the effects of Tirz, Sema, and Reta on Non-Alchoolic Fatty Liver Disease and they all helped but Reta was the best one.
Not sure about this one so take it with a grain of salt and find the actual study.
 
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I dont think any source carries Pem yet.

I believe that Pem is equally split between GLP1 and GCGR whereas Reta is higher GIP and the remainder balanced between GLP1 and GCGR. (Someone please correct me if i'm wrong). That would mean that Pem has higher GCGR (vs Ret) and that the lean loss isnt due to GCGR? It should not be due to GIP either because Tirz has much higher GIP (vs GLP1).

Could the difference in lean loss be due to Pem having a longer half life (7d vs Tirz and Reta) and that the doses in Reta were escalated too quickly (36 weeks study)?
 
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I dont think any source carries Pem yet.

I believe that Pem is equally split between GLP1 and GCGR whereas Reta is higher GIP and the remainder balanced between GLP1 and GCGR. (Someone please correct me if i'm wrong). That would mean that Pem has higher GCGR (vs Ret) and that the lean loss isnt due to GCGR?

Could the difference in lean loss be due to Pem having a longer half life (7d vs Tirz and Reta) and that the doses in Reta were escalated too quickly (36 weeks study)?

Looks very promising. I wonder if nausea will be more pronounced like Sema, since GIP has an antiemetic (anti-nausea) effect via the brain. I think Sema's stronger nausea actually helps promote faster weight loss vs Tirz/Reta, even though they ultimately lead to more total weight loss.
 
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I dont think any source carries Pem yet.

I believe that Pem is equally split between GLP1 and GCGR whereas Reta is higher GIP and the remainder balanced between GLP1 and GCGR. (Someone please correct me if i'm wrong). That would mean that Pem has higher GCGR (vs Ret) and that the lean loss isnt due to GCGR? It should not be due to GIP either because Tirz has much higher GIP (vs GLP1).

Could the difference in lean loss be due to Pem having a longer half life (7d vs Tirz and Reta) and that the doses in Reta were escalated too quickly (36 weeks study)?
The difference is because they’re pretending that MRI scans and DEXA scans are measuring the same thing. And they’re pretending that you can make a meaningful comparison between different drugs by looking at an obesity trial for one and a diabetes trial for another. Bonus points because they did both of these things at the same time.

This is all nonsense to hype investors.
 
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Wasn't the loss of lean mass just due to calorie deficit and lower protein intake without resistance training? I'd think that lean mass loss would just increase with longer duration of the treatmenet and higher doses/stronger drugs because of prolonger/steeper deficit and lower protein.
Or do GLPs have a direct effect on muscle mass?
Also they are using MRIs and DEXAs to determine muscle loss and fat loss. A lot of that apparent muscle loss could just be loss of glicogen and intra-muscular water because of calorie deficit.
A better metric to determin muscle loss would be to test muscle strenght (like grip strengh, leg extension strenght, chest press 1rm strenght, etc).

Also the different agonim of the different drugs will probably have different outcomes. Sema probably causes the most nause and therefore people will probably be more incline to eat more palatable food (that are lower protein and higher fat/sugar), while the less nausea from tirz/reta and the fact that they also decrease the general desire for pleasure (junk food, alchool, sigarettes, drugs, porn) might make people eat simpler food that also happen to be more nutrient densne/higher protein.
It's all speculation tho.
I personally noticed that sema (I had an ozempic pen like 2 years ago to try) gave me terrible nausea and stomach pain but mentally I still had cravings, only used it for 2 weeks and gave up.
This time with tirz I have gotten no side effects and mentally I feel much less inclined to eat. Even when phisically hungry I can just choose to not eat and feel fine.
Might be the agonism of different receptors has different effects on the body/brain and it's way of dealing with food.
 
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This was published by Altimmune in Jan 2025.
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I dont think any source carries Pem yet.

I believe that Pem is equally split between GLP1 and GCGR whereas Reta is higher GIP and the remainder balanced between GLP1 and GCGR. (Someone please correct me if i'm wrong). That would mean that Pem has higher GCGR (vs Ret) and that the lean loss isnt due to GCGR? It should not be due to GIP either because Tirz has much higher GIP (vs GLP1).

Could the difference in lean loss be due to Pem having a longer half life (7d vs Tirz and Reta) and that the doses in Reta were escalated too quickly (36 weeks study)?
The lean mass lost is mostly all bullshit in these trials because they haven't checked it on ppl resistance training and eating healthy food with good amount of protein.

There are few big users here smashing 10/15mg of reta and tirz and sure as hell they ain't losing muscle xD

Of course if you starve yourself you are gonna lose muscle and fat....it's not like glp-1 are muscle sparing like some fat burner substances.
 
The lean mass lost is mostly all bullshit in these trials because they haven't checked it on ppl resistance training and eating healthy food with good amount of protein.

There are few big users here smashing 10/15mg of reta and tirz and sure as hell they ain't losing muscle xD

Of course if you starve yourself you are gonna lose muscle and fat....it's not like glp-1 are muscle sparing like some fat burner substances.
I suspect a lot of that "muscle loss" is actually glicogen and intramuscular water loss. If you were at maintnance/surplus and got a dexa scan, then went into a deficit for 4-6week and got another the scan would show a significat muscle loss, but in reality that's mostly water and glicogen.
These people are probably still loosing muscle because of low calories and low protein, but not as much as it appears
 
Wasn't the loss of lean mass just due to calorie deficit and lower protein intake without resistance training? I'd think that lean mass loss would just increase with longer duration of the treatmenet and higher doses/stronger drugs because of prolonger/steeper deficit and lower protein.
Or do GLPs have a direct effect on muscle mass?
Also they are using MRIs and DEXAs to determine muscle loss and fat loss. A lot of that apparent muscle loss could just be loss of glicogen and intra-muscular water because of calorie deficit.
A better metric to determin muscle loss would be to test muscle strenght (like grip strengh, leg extension strenght, chest press 1rm strenght, etc).

Also the different agonim of the different drugs will probably have different outcomes. Sema probably causes the most nause and therefore people will probably be more incline to eat more palatable food (that are lower protein and higher fat/sugar), while the less nausea from tirz/reta and the fact that they also decrease the general desire for pleasure (junk food, alchool, sigarettes, drugs, porn) might make people eat simpler food that also happen to be more nutrient densne/higher protein.
It's all speculation tho.
I personally noticed that sema (I had an ozempic pen like 2 years ago to try) gave me terrible nausea and stomach pain but mentally I still had cravings, only used it for 2 weeks and gave up.
This time with tirz I have gotten no side effects and mentally I feel much less inclined to eat. Even when phisically hungry I can just choose to not eat and feel fine.
Might be the agonism of different receptors has different effects on the body/brain and its way of dealing with food.
It’s helpful to understand what “lean mass” is. Our friends at Altimmune helpfully provided MRI scan data for body composition changes with Pemvidutide. Maybe other pharma companies could do the same, that would be nice. MRIs provide quite nice specificity about that.

Altimmune is comparing their MRI scan data to DEXA scan data. DEXA scans are cheap and easy, but they’re also not nearly as specific about what they’re seeing when assessing body composition. Everything gets lumped into three categories: bone mass, fat mass, and lean mass. Lean mass is a category where they shove everything they can’t put in the first two categories.

So let’s look at things you might not expect to be in the lean mass category.

Liver fat is a great example to start with. While DEXA scans can identify subcutaneous fat and visceral fat, they can’t separate liver fat from the lean mass of the liver. So your liver fat is “lean mass”. So when you take a drug like Reta that causes a 90% reduction in liver fat you and then do a DEXA scan that gets recorded as “lean mass loss”. But when you take a drug like Pemvidutide that also causes significant reduction in liver fat and then do an MRI scan, that gets recorded as “fat loss”. Same issue with pancreatic fat. Same issue with cardiac fat.

Ever have a nice steak with all the marbling? That’s intramuscular fat. Aka “lean mass” according to DEXA. So when we reduce the amount of intramuscular fat and take a DEXA scan that’s “lean mass loss” but if we reduce the amount of intramuscular fat and take an MRI scan that’s “fat loss”.

There’s several more types of fat that DEXA lumps into the “lean mass” category. But let’s go back to liver fat and think about how our friends at Altimmune are comparing their obesity trial to a Reta diabetes trial. Diabetics have screwed up metabolisms and as a result tend to have pronounced issues with fatty liver. So you’d expect more “lean mass loss” by eliminating that fat in a diabetic patient than you’d get by eliminating it in a non-diabetic one.

What about other things that aren’t fat and aren’t muscle in the lean mass category? Water is a big one. It turns out that when you’re type 2 diabetic and have issues with chronic hyperglycemia, you retain a lot of water due to osmotic gradients from the glucose elevation. You retain even more water because you also have chronic hyperinsulinemia. An MRI can distinguish water from skeletal muscle but on a DEXA scan it’s all just “lean mass”. So when you’re a type 2 diabetic and you take a fancy diabetes drug, fix your insulin resistance, and revert to normoglycemia, all of that water retention goes away. Hooray. And if you’re on Reta and take a DEXA scan, that’s the dreaded “lean mass loss” but if you’re on Pem and get the complimentary MRI scan it’s just water reduction.

You’ve also got a bunch of water in your muscles, right? The easiest way to goose your DEXA scan results is to not take creatine for your baseline scan and start taking it afterwards. Woohoo, instant lean mass gains. If you’re on a mild diuretic drug like Reta or Pem, you might expect some fluid loss there as well. And if you’re on an anorectic like Reta or Pem you might expect a decrease in your muscular glycogen (mostly water) stores. And if you’re on a GCGRA like Reta or Pem you might expect a decrease in hepatic glycogen stores. If you do a DEXA scan that’s “lean mass loss” but the MRI just sees a fluid shift.

So that’s what I mean when I say this is a completely worthless comparison and Altimmune should be ashamed to even make it. Hopefully they got the stock pump they were after.
 
It’s been about two weeks into my first run with Tirz at 1mg EOD (3.5mg per week).

I haven’t experienced any appetite suppression, though that’s not my primary reason for taking it. I also haven’t noticed any improvements in my blood glucose levels at this dosage.

The only notable change is that I’ve completely lost the urge to eat junk food, even during my off-season/push phase. I used to snack between meals and enjoy the occasional sweet, but that desire is entirely gone. Additionally, my sleep quality has significantly improved since starting Tirz.

I plan to stick with 1mg every other day until I begin cutting, as I don’t want to suppress my appetite too much. I also have Reta on the way, which I’ll likely incorporate during the second half of my cut phase.
 
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