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?

 

[egruberman]

There are a few off the top of my head. Atrial structure improvement, that is the reversal of long term damage from stresses, is pronounced in normal weight, non-diabetics but not the obese.

If you can think of any that tease apart the effect independent from weight loss and metabolic improvement I’d like to see them.

To be clear, he made the assertion and it was qualified. I am passing it along as a point of interest, but may be interpreting his statements incorrectly.

 

[Musmadar]

While much of the conversation surrounding these drugs focuses on their ability to suppress appetite, there is far more to their benefits. For those dedicated to optimizing their health and performance, tirzepatide and retatrutide offer a range of metabolic improvements that go beyond simple caloric restriction:

One of the most important effects of both tirzepatide and retatrutide is their role in improving insulin sensitivity, improved insulin sensitivity means better glucose uptake by muscle cells, leading to more efficient use of carbohydrates consumed post-exercise. This promotes faster recovery, greater glycogen replenishment, and enhanced muscle growth over time.

When the body is more sensitive to insulin, less of the hormone is required to keep blood sugar levels stable, which in turn reduces the risk of insulin resistance—a precursor to type 2 diabetes, this means that they can maintain higher energy levels during workouts and optimize muscle growth, while simultaneously reducing the risk of developing metabolic diseases.

In addition to enhancing insulin sensitivity, tirzepatide and retatrutide can significantly improve how the body processes and uses carbohydrates. Proper carbohydrate metabolism ensures that glucose is effectively used during exercise, delaying the onset of fatigue and allowing for longer, more intense sessions.

Moreover, post-exercise, efficient carbohydrate utilization aids in faster glycogen restoration in muscles, which is essential for recovery and the ability to perform optimally in subsequent workouts. This improvement in metabolic function means that the nutrients consumed are put to better use in fueling performance and muscle repair.

While the appetite-suppressing effects of tirzepatide and retatrutide are often highlighted, their impact on fat loss goes far beyond simply reducing caloric intake. These drugs can promote fat loss by improving overall metabolic health. By increasing insulin sensitivity and optimizing carbohydrate use, the body becomes more efficient at burning fat for energy, especially in a caloric deficit.

Moreover, these drugs may enhance the body's thermogenic capacity, further supporting fat loss. By increasing the energy expenditure even at rest, tirzepatide and retatrutide allow individuals to burn more calories throughout the day, contributing to a leaner physique over time.

Another key benefit of tirzepatide and retatrutide is their ability to reduce inflammation, which is crucial for both short-term performance and long-term health. Intense exercise, particularly in strength training or endurance sports, can lead to temporary increases in inflammation. While this is a natural part of the recovery process, chronic inflammation can hinder progress and increase the risk of injuries or illnesses.

By improving insulin sensitivity and stabilizing blood sugar levels, tirzepatide and retatrutide help reduce chronic inflammation. This supports faster recovery, improved joint health, and greater resilience in training. Additionally, these drugs have been shown to improve lipid profiles and cardiovascular health, reducing the risk of heart disease—a critical point for anyone involved in long-term bodybuilding.

These medications address the root causes of metabolic dysfunction, offering improvements in insulin sensitivity, carbohydrate utilization, fat loss, and inflammation management.

 

[Sampei]

Tirz is better on paper and the general anecdotal consensus is that it just lacks the HEAVY appetite suppression Sema has. So it depends what you want to use it for, appetite control and some health benefits or maximum efficacy on the health and medium appetite control?

To me the complete opposite sema gas some appetite control at first but after just a bit I get used to it and it gives me no side at all plus the glycemic control of sema Is superior for me.

Tirz destroyed my gastric emptiness, I could feel full for hours after eating just a little snack. Food craving? 0. Appetite average but as I felt full all the time I didn't want to eat.
Glycemic control of tirz on 5mg? Not that great.

 

[HB_22]

I

would really like to get the binding affinity for each nailed down on a relative basis to one another. Feel like I saw it somewhere but could never find it again.

Please dont mix up binding affinity with receptor activation. You can have a very strong binding affinity but still very low to almost no receptor activation, as this is how most antidotes work.

 

[Trenbolonetax]

Please dont mix up binding affinity with receptor activation. You can have a very strong binding affinity but still very low to almost no receptor activation, as this is how most antidotes work.

I did mix those up. Thank you for the correction! If I could find that, I would be very happy.

No other reason than curiosity. So far, I am having my best experience on Reta.

 

[Sampei]

My understanding is that reta has a greater binding affinity to GLP1 and GIP than tirz, in addition to the glucagon effect.



Semaglutide has a much greater binding affinity to GLP1 than tirzepatide and retatrutide. Theoretically then, one could add it in to a stack, but there are potential downsides to this and nothing in the literature that supports it. As @Ghoul stated, it's probably best to stick with a single compound for as long as its effective, which for most, should be indefinitely.

Peter Attia just did an AMA on GLP-1 agonists:

#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape - Peter Attia

"If you're taking these drugs, really, really pay attention to your protein consumption and your resistance training. . .that's obviously going to be an important part of being on the right side of that body composition curve.” — Peter Attia

peterattiamd.com

It's an interesting summary of the literature. The only point that I found particularly interesting was that there is no evidence (according to him) of any health benefit of a GLP1 agonist independent of the effect on body composition and metabolic improvements.

Some other points:
There's more safety data and nothing to suggest any issues with these compounds.
Most likely they should be taken indefinitely and there's no real observed reduction in efficacy, provided they aren't used intermittently.

He points to the SELECT trial which shows no weight regain with semaglutide when continued over the course of four years:

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial - Nature Medicine

A prespecified analysis of the SELECT trial revealed that patients assigned to once-weekly subcutaneous semaglutide 2.4 mg lost significantly more weight than those receiving placebo and showed improvements in various anthropometric indices.

www.nature.com

There's some other stuff in there. It's a good listen if you have a subscription, but I think nothing that would surprise any of us.

What's the downside for example of using 0.5mg sema and 2.5mg of Tirz instead of maybe 1mg sema alone or 5mg Tirz alone?

 

[Sampei]

While much of the conversation surrounding these drugs focuses on their ability to suppress appetite, there is far more to their benefits. For those dedicated to optimizing their health and performance, tirzepatide and retatrutide offer a range of metabolic improvements that go beyond simple caloric restriction:

One of the most important effects of both tirzepatide and retatrutide is their role in improving insulin sensitivity, improved insulin sensitivity means better glucose uptake by muscle cells, leading to more efficient use of carbohydrates consumed post-exercise. This promotes faster recovery, greater glycogen replenishment, and enhanced muscle growth over time.

When the body is more sensitive to insulin, less of the hormone is required to keep blood sugar levels stable, which in turn reduces the risk of insulin resistance—a precursor to type 2 diabetes, this means that they can maintain higher energy levels during workouts and optimize muscle growth, while simultaneously reducing the risk of developing metabolic diseases.

In addition to enhancing insulin sensitivity, tirzepatide and retatrutide can significantly improve how the body processes and uses carbohydrates. Proper carbohydrate metabolism ensures that glucose is effectively used during exercise, delaying the onset of fatigue and allowing for longer, more intense sessions.

Moreover, post-exercise, efficient carbohydrate utilization aids in faster glycogen restoration in muscles, which is essential for recovery and the ability to perform optimally in subsequent workouts. This improvement in metabolic function means that the nutrients consumed are put to better use in fueling performance and muscle repair.

While the appetite-suppressing effects of tirzepatide and retatrutide are often highlighted, their impact on fat loss goes far beyond simply reducing caloric intake. These drugs can promote fat loss by improving overall metabolic health. By increasing insulin sensitivity and optimizing carbohydrate use, the body becomes more efficient at burning fat for energy, especially in a caloric deficit.

Moreover, these drugs may enhance the body's thermogenic capacity, further supporting fat loss. By increasing the energy expenditure even at rest, tirzepatide and retatrutide allow individuals to burn more calories throughout the day, contributing to a leaner physique over time.

Another key benefit of tirzepatide and retatrutide is their ability to reduce inflammation, which is crucial for both short-term performance and long-term health. Intense exercise, particularly in strength training or endurance sports, can lead to temporary increases in inflammation. While this is a natural part of the recovery process, chronic inflammation can hinder progress and increase the risk of injuries or illnesses.

By improving insulin sensitivity and stabilizing blood sugar levels, tirzepatide and retatrutide help reduce chronic inflammation. This supports faster recovery, improved joint health, and greater resilience in training. Additionally, these drugs have been shown to improve lipid profiles and cardiovascular health, reducing the risk of heart disease—a critical point for anyone involved in long-term bodybuilding.

These medications address the root causes of metabolic dysfunction, offering improvements in insulin sensitivity, carbohydrate utilization, fat loss, and inflammation management.

Sema has a great glycemic control too and it last 7 days something that Tirz can't do as it's 5 days half life really decrease the glycemic control on the last few days before the new dose is injected.

Diabetic friends report a lot better glycemic control and less need of insulin on semaglutide 1mg for example compared to Tirz at 7.5mg.

I believe we are forgetting about sema just because ppl are getting hyped up on Tirz and reta.

Sema price is super low at the moment compared even to Tirz and ppl in my opinion should first see if sema works for them before jumping on the tirz bandwagon

 

[Ghoul]

What's the downside for example of using 0.5mg sema and 2.5mg of Tirz instead of maybe 1mg sema alone or 5mg Tirz alone?

While part of me appreciates the willingness of people to make themselves human guinea pigs, once again my question, without any ability to quantify the risk of using these drugs together, what is it that the thoroughly tested, safe protocols of using one fails to provide? As eguberman pointed out, over 3+ years of use, they're more effective for 99.9% of users than could've been dreamed of a decade ago.

What are you gaining by trying random combinations of these molecules?

As far as specific risks, I could put theoretical ones out there, based on facts, but no one's out there conducting these experiments, since there's still so much to learn about the compounds individually.

 

[Musmadar]

Sema has a great glycemic control too and it last 7 days something that Tirz can't do as it's 5 days half life really decrease the glycemic control on the last few days before the new dose is injected.

Diabetic friends report a lot better glycemic control and less need of insulin on semaglutide 1mg for example compared to Tirz at 7.5mg.

I believe we are forgetting about sema just because ppl are getting hyped up on Tirz and reta.

Sema price is super low at the moment compared even to Tirz and ppl in my opinion should first see if sema works for them before jumping on the tirz bandwagon

Sema was the first reson for me to dive into the Glp's agonists waters....

After years of trying almost all the others insulin sensitivity related enhancers like:
metformin, chromium, berberine, cinamon, sibutramine, intermitent fasting....you name it,
when I tryed sema I could almost feel it's effect like a pumping effect to all my muscles and extremities....I knew it's something very good happening.

I didn't mind the little nausea either because of its others beneficial effects.

You are right: with the actual lowered price it's, maybe the best choice among the other glp's agonists.

 

[Ghoul]

Sema was the first reson for me to dive into the Glp's agonists waters....

After years of trying almost all the others insulin sensitivity related enhancers like:
metformin, chromium, berberine, cinamon, sibutramine, intermitent fasting....you name it,
when I tryed sema I could almost feel it's effect like a pumping effect to all my muscles and extremities....I knew it's something very good happening.

I didn't mind the little nausea either because of its others beneficial effects.

You are right: with the actual lowered price it's, maybe the best choice among the other glp's agonists.

Sema is incredible bang for the buck. About $2 a week at the max dose.

Tirz is a "premium" option in my mind, much gentler, though the majority of non weight related benefits really seem to require the 15mg dose, so it's $15-20 a week at the best current prices.