MESO-Rx Exclusive Ozempic and Mounjaro for bodybuilders - more than just weight loss drugs

[MESO-Rx Administrator]

@Type-IIx explains the benefits of GLP-1 and GIP agonists like Semaglutide and Tirzepatide, as true insulin sensitizing agents. how they are different from other weight loss drugs, and the benefits as partitioning agents for bodybuilders.

I'm sure you've read a lot about Ozempic, Wegovy, and Mounjaro for overweight sedentary people in the mainstream media but if you want to read about the use of these drug from a bodybuilding perspective, read on:

Semaglutide and Tirzepatide are More Than Just Weight Loss Drugs

Learn how GLP-1 and GIP agonists like Semaglutide and Tirzepatide enhance insulin sensitivity, preserve muscle mass and reduce fat stores.

thinksteroids.com

 

[Type-IIx]

Thanks, Millard!

New article for the Meso readership!j In this article, I make the case for incretin drugs as (note: mild!) partitioning agents.

I do not intend to make the case that incretins are as potent as Clen (clenbuterol HCl) which is, per-mg, more potent than testosterone in its anabolic effects (and enhancement of muscle power & strength and sprint perofrmance) albeit subject to a rapid diminution in this effect with time (due to β₂AR tachyphylaxis or desensitization), and subject to a threshold or ceiling at which side effects outweight benefits.

I do not intend to make the case that incretin drugs can overcome severe energy deficits (i.e., kcal restriction) & protein deficiency to enhance recomp or cutting!

Sections:
1. Recomp vs. Partitioning, and the concept of the p-ratio explained, including explanations of insulin resistance vs. sensitivity and the importance of leptin and hormones
2. Incretins: GLP-1 & GIP agonists, and how they serve to enhance insulin sensitivity
4. Lipolytic agents: why drugs like clen & stimulants like ephedrine work for fat loss although they cause insulin resistance
5. Evidence that incretins enhance body composition by maintaining FFMI & skeletal muscle index & preferentially reduce fat stores, even in instances devoid of resistance training and controlled nutritional adherence to high protein ingestion & modest deficits (that you must practice for any substantial recomp effect)
6. Distinction between insulin resistance & hyperglycemia (common bodybuilding misunderstandings of IR)
7. How exogenous insulin (slin) worsens insulin sensitivity despite ameliorating hyperglycemia.

 

[AlexDavis43]

Great article, thanks.

This part: "Insulin resistance enhances fat loss (decreased FM), but at the expense of retention of LBM (thus is irrational for sane cutting)."

Insulin resistance in adipocytes, yes, but that happens long after skeletal muscle insulin resistance. So it is somewhat misleading or missing necessary context details.

So long after you get obese, a mechanism to prevent you from keep getting obeser.

 

[AlexDavis43]

"When tissues like the liver and fat cells fail to be stimulated by insulin, glucose is not taken up by the cells. Without glucose, the liver begins to metabolize free-fatty acids (FFAs), thereby increasing ketone levels in the blood, preventing them from being re-esterified into fat cell"

But this is in obesity, and doesn't lead to fat loss. And obese people aren't in ketosis. What's the disconnect(s) here?

 

[AlexDavis43]

Interesting comparison of testosterone and insulin. Testosterone undecanoate is all the rage these days for TRT but it is the complete opposite of circadian rhythms of testosterone exposure.

100% convenience, 0% physiology

First phase insulin response is seems to fail early in the etiology of T2DM.

 

[Spaceman Spiff]

As always I appreciate the articles.


I have been on Tirzepatide 7.5mg a week for some time. I re-added growth and on a low dose cycle. 200 test, 300 mast and am noticing some phenomenal size growth.

 

[Type-IIx]

Great article, thanks.

This part: "Insulin resistance enhances fat loss (decreased FM), but at the expense of retention of LBM (thus is irrational for sane cutting)."

Insulin resistance in adipocytes, yes, but that happens long after skeletal muscle insulin resistance. So it is somewhat misleading or missing necessary context details.

So long after you get obese, a mechanism to prevent you from keep getting obeser.

"When tissues like the liver and fat cells fail to be stimulated by insulin, glucose is not taken up by the cells. Without glucose, the liver begins to metabolize free-fatty acids (FFAs), thereby increasing ketone levels in the blood, preventing them from being re-esterified into fat cell"

But this is in obesity, and doesn't lead to fat loss. And obese people aren't in ketosis. What's the disconnect(s) here?

Very astute reading! I think that the disconnect is that you may be coming from the perspective of thinking in terms of disease states (e.g., the factors involved in the "deadly triad" and T2DM) whereas this article is aimed at drug effects (i.e., lipolytic agents; e.g., rhGH & its stimulating HSL). Specifically, when I write this, I am taking aim at those who advocate for frequent rhGH administration rather than infrequent because IR "benefits" lipolysis.

The latter point with respect to ketosis, that more describes DKA. But, doesn't ketosis to some degree lead to some incrementally greater fat loss as a result of this process?

 

[AlexDavis43]

Very astute reading! I think that the disconnect is that you may be coming from the perspective of thinking in terms of disease states (e.g., the factors involved in the "deadly triad" and T2DM) whereas this article is aimed at drug effects (i.e., lipolytic agents; e.g., rhGH & its stimulating HSL). Specifically, when I write this, I am taking aim at those who advocate for frequent rhGH administration rather than infrequent because IR "benefits" lipolysis.

The latter point with respect to ketosis, that more describes DKA. But, doesn't ketosis to some degree lead to some incrementally greater fat loss as a result of this process?

Thank you, sir.

Ketosis means elevated hepatic partial fatty acid oxidation which doesn't contribute as much quantitatively to total body fat oxidation as skeletal muscle [complete] fatty acid oxidation.

I think I agree but people in ketosis can be in positive energy balance and gain body fat (so fat loss is likely but not guaranteed).

 

[Type-IIx]

Thank you, sir.

Ketosis means elevated hepatic partial fatty acid oxidation which doesn't contribute as much quantitatively to total body fat oxidation as skeletal muscle [complete] fatty acid oxidation.

I think I agree but people in ketosis can be in positive energy balance and gain body fat (so fat loss is likely but not guaranteed).

Yes, we probably agree since I agree that energy state is always controlling; and certainly in obesity, fat loss will not occur as a result of ketosis per se.

 

[MB101]

As always I appreciate the articles.


I have been on Tirzepatide 7.5mg a week for some time. I re-added growth and on a low dose cycle. 200 test, 300 mast and am noticing some phenomenal size growth.

I was considering something similar but wasn’t sure if I’d be able to get in my calories. Figured I would have to drop the Tirz if I cant eat right. How is feeding going are you in a small surplus.

 

[Spaceman Spiff]

I was considering something similar but wasn’t sure if I’d be able to get in my calories. Figured I would have to drop the Tirz if I cant eat right. How is feeding going are you in a small surplus.

going on a small surplus. I typically go protein heavy if anything.

it does feel like the GH is keeping glycogen load high for sure

 

[Spaceman Spiff]

If does seem like a safer option than tren for a non competitor/harm reduction (although pricier)

 

[Saints2016]

As always I appreciate the articles.


I have been on Tirzepatide 7.5mg a week for some time. I re-added growth and on a low dose cycle. 200 test, 300 mast and am noticing some phenomenal size growth.

Curious how much you’re eating? Is it curbing your appetite and you need to force feed yourself?

 

[Spaceman Spiff]

Curious how much you’re eating? Is it curbing your appetite and you need to force feed yourself?

I can control it

 

[Musmadar]

As always I appreciate the articles.


I have been on Tirzepatide 7.5mg a week for some time. I re-added growth and on a low dose cycle. 200 test, 300 mast and am noticing some phenomenal size growth.

I am on a path to become type II diabetic (prediabetic)...
Your scheme of PED's seems the way to adopt for me.
Just wanted to let you know that I'm interested in your progress.

 

[Jin23]

Incretins (GLP-1 and GIP agonists) directly enhance insulin sensitivity by modulating insulin secretion

Don't you find the statement that glp-1 agonist are "true insulin sensitizing agents" or that they "improve insulin sensitivity" too misleading?

A true insulin sensitizing agent (like cinnamon for example) would either increase the number of insulin receptors or improve the signaling pathway downstream of the insulin receptor, thus enhancing the cell's response to insulin. Per my knowledge, GLP-1's don't increase GLUT-4 translocation, phosphorylation and they don't enhance PI3K, AKT, etc. nor do they really inhibit the activity of enzymes or processes that work against insulin signaling. The only MOA of indirectly improving insulin sensitivity seems to be a reduction in inflammation, due to a decrease in proinflammatory cytokines (and possibly some microbiome alterations).

An increase in insulin sensitivity implies that per the same unit of insulin, we would see improvements in BG control, so either insulin sensitivity is a more encompassing term than I'm imagining or the term is being used too liberal. Wouldn't you agree that a term like "increasing insulin signaling" is more appropriate or just "improving glucose control"?

Putting it simply, is this just a case of perspective, ie. if one is only monitoring BG levels, a reduction of BG would imply increased insulin sensitivity, but if one was to monitor BG and fasting insulin levels (or perform OGTT with insulin monitoring), "increased insulin sensitivity" would not be the conclusion one would derive at ...

Interested in your thoughts.

 

[29trt]

Don't you find the statement that glp-1 agonist are "true insulin sensitizing agents" or that they "improve insulin sensitivity" too misleading?

A true insulin sensitizing agent (like cinnamon for example) would either increase the number of insulin receptors or improve the signaling pathway downstream of the insulin receptor, thus enhancing the cell's response to insulin. Per my knowledge, GLP-1's don't increase GLUT-4 translocation, phosphorylation and they don't enhance PI3K, AKT, etc. nor do they really inhibit the activity of enzymes or processes that work against insulin signaling. The only MOA of indirectly improving insulin sensitivity seems to be a reduction in inflammation, due to a decrease in proinflammatory cytokines (and possibly some microbiome alterations).

An increase in insulin sensitivity implies that per the same unit of insulin, we would see improvements in BG control, so either insulin sensitivity is a more encompassing term than I'm imagining or the term is being used too liberal. Wouldn't you agree that a term like "increasing insulin signaling" is more appropriate or just "improving glucose control"?

Putting it simply, is this just a case of perspective, ie. if one is only monitoring BG levels, a reduction of BG would imply increased insulin sensitivity, but if one was to monitor BG and fasting insulin levels (or perform OGTT with insulin monitoring), "increased insulin sensitivity" would not be the conclusion one would derive at ...

Interested in your thoughts.

Sorry to butt in but from my personal experimentation on exactly this topic I can safely say that semaglutide is not insulin sensitising in any way except indirectly by reducing calorie intake.
with 1mg/week during months I kept the same calorie intake and mantained the same weight and guess what... my fasted BG stayed the same and so did my postprandial taken at 30min intervals for 2h...
As soon as I decreased carb intake I immediately saw BG nb. drop.
Would a higher dose produce the same results..? maybe... wll have to try that some other time

the claims made are also contradictory as they imply insulin sensitising and in the same breath say that it stimulates insulin production so even if it is increasing insulin sensitivity by some mechanisms the effect is counteracted by more insulin production... which might help a T2D pacient... hence why it was originally designed for...

 

[Jin23]

Sorry to butt in but from my personal experimentation on exactly this topic I can safely say that semaglutide is not insulin sensitising in any way except indirectly by reducing calorie intake.
with 1mg/week during months I kept the same calorie intake and mantained the same weight and guess what... my fasted BG stayed the same and so did my postprandial taken at 30min intervals for 2h...
As soon as I decreased carb intake I immediately saw BG nb. drop.
Would a higher dose produce the same results..? maybe... wll have to try that some other time

the claims made are also contradictory as they imply insulin sensitising and in the same breath say that it stimulates insulin production so even if it is increasing insulin sensitivity by some mechanisms the effect is counteracted by more insulin production... which might help a T2D pacient... hence why it was originally designed for...

Yes.

Btw, if you want to gauge insulin sensitivity, it would be much more prudent to use fasting insulin as a biomarker. BG is much higher in the hierarchy of glucose management cascade and is influenced by to many factors to make it a usable biomarker for insulin sensitivity.

 

[29trt]

Yes.

Btw, if you want to gauge insulin sensitivity, it would be much more prudent to use fasting insulin as a biomarker. BG is much higher in the hierarchy of glucose management cascade and is influenced by to many factors to make it a usable biomarker for insulin sensitivity.

Yeah I am aware of that and have attempted to measure insulin level but the lab I was using for bloodwork sends the blood sample to another lab for the insulin test and as you know both BG and insulin degrade with time if no measures are taken to preserve the sample .
I took two different blood samples before the Sema experiment and during both fasted in the morning the first one was very low basically under the detectable range and second one was higher and seemed normal but I cannot be certain it was correct.
I inquired about their methods to preserve the samples but I have not received a reply . I found about the degradation after the fact so it kind ruined my experiment but still if a meaningful insulin sensitizing effect was at play I would expect BG to reflect that especially the postprandial .

 

[Jin23]

but still if a meaningful insulin sensitizing effect was at play I would expect BG to reflect that especially the postprandial .

If you're still talking about using a glp-1 agonist?, then I disagree, off course. This whole conversation was pinpointing the exact same issue which you choose to disregard in your last statement. Seeing how glp-1 agonists increase insulin secretion, fasting blood glucose measurements can't be used as a marker for insulin sensitivity. You'd have to be a type 1 diabetic, with complete beta cell dysfunction and then add a glp-1 agonist, all the while keeping the insulin at an exactly the same dose. But even such an experiment would be fraud with errors and the final conclusion would be a guessing game (if bg was the only biomarker) just the same, albeit to lesser degree.