GLP-1 agonists: Roughly half of the pounds lost are in the form of muscle protein

[Millard]

I saw this in a recent article by Patrick Arnold:

"GLP-1 agonists were a breakthrough in obesity treatment as no other obesity drugs ever came close to delivering the dramatic weight loss that they could. There is one problem with GLP-1 agonist promoted weight loss though, and that is the fact that roughly half of the pounds lost are in the form of muscle protein. This is not the healthiest of things, nor is it an optimally desired outcome cosmetically speaking."

https://www.patreon.com/posts/new-muscle-drug-91899603

 

[Millard]

I can see this being the next craze.

I think BioAge Labs is doing everything they can to make sure it is. Their promotional graphics promise that stacking their Azelaprag with Mounjaro will turn you into a lean muscular bodybuilder with an eight-pack! Whereas tirezepatide only makes you skinny!


GLP-1 aone vs. GLP-1 + BGE-105

It makes sense for people who are overweight and don't exercise. They take a drug that makes it easy for them to starve themselves, continue to not exercise, and lose mass of every kind.

 

[Type-IIx]

I think BioAge Labs is doing everything they can to make sure it is. Their promotional graphics promise that stacking their Azelaprag with Mounjaro will turn you into a lean muscular bodybuilder with an eight-pack! Whereas tirezepatide only makes you skinny!

View attachment 269452
GLP-1 aone vs. GLP-1 + BGE-105

Domain Name: THINKSTEROIDS.COM
...
Registrant Name: Contact Privacy Inc...
Registrant Organization: Contact Privacy Inc...
Registrant Street: 96 Mowat Ave
Registrant City: Toronto
Registrant State/Province: ON
Registrant Postal Code: M6K 3M1
Registrant Country: CA

Domain Name: bioagelabs.com
...
Registrant Name: Contact Privacy Inc...
Registrant Organization: Contact Privacy Inc...
Registrant Street: 96 Mowat Ave
Registrant City: Toronto
Registrant State/Province: ON
Registrant Postal Code: M4K 3K1
Registrant Country: CA

The plot thickens! Are Millard and Patrick Arnold the mystery labcoats behind this product?!

Or, do you agree with the boring skeptics that Contact Privacy is simply a widely used service?

I think we should apply the opposite of Occam's Razor here, and go with the more elaborate conspiracy. It's way more interesting!

 

[Millard]

I think we should apply the opposite of Occam's Razor here, and go with the more elaborate conspiracy. It's way more interesting!

WTF, I don't know what you're doing exposing my Canadian connections here. It makes it harder to explain the recently uncovered grainy photo of me chillin with the Mounties carrying sledgehammers, obviously up to no-good!

 

[Fattyone]

I saw an article on Apple News this morning (behind a paywall unfortunately) that had been titled roughly “ozempec and testosterone, the ultimate get lean combo”.
Weird to see this stuff so mainstream.

 

[Type-IIx]

WTF, I don't know what you're doing exposing my Canadian connections here. It makes it harder to explain the recently uncovered grainy photo of me chillin with the Mounties carrying sledgehammers, obviously up to no-good!

View attachment 269485

Oh. My. God. This smoking gun makes it obvious that we are unraveling a shadowy syndicate whose tentacles have international reach and that corrupt officials with ease, all for the nefarious ends of delivering 8-pack abs. Speaking of which, sick core development bro!

 

[Spaceman Spiff]

corrupt officials with ease, all for the nefarious ends of delivering 8-pack abs.

 

[Type-IIx]

View attachment 269531

He shops where villains shop, clearly.

 

[Mac11wildcat]

Almost as if your body doesn’t respond well to drastically reducing macro and micronutrient intake because you took the new wonderdrug instead of changing habits.

 

[Bulacanboi]

I have lost 65 pounds with the help of a Tirz. and I haven't really lost much muscle. Granted, i am taking 200mg test, 200mg Primo a week, and 4iu of HGH ed. My results have been really really good. I highly recommend it. In fact i think it should be free to everyone, think of all the healthcare savings we would enjoy, in USA, if we reduced the obese population

I think most of this community are using the glps to religiously stick to their planned prep/cut diet and just mitigate the hunger variable so they can sleep better and only eat enough to not break down much if any muscle. I usually can only stick to about .75-1.0lbs a week weight loss but with tirz I can stick to losing 1.5-2.0 lb a week and its easy. If I go more than 2lbs a week the fatigue takes over and I will just get hurt in the gym and not recover well. I think its just another variable to push and optimize, some folks dont want to use clen or stimulants or hgh, so more options more better. I do 1.2g/lb daily protein and haven't lost any measurable strength in the gym, If I have lost lean mass I dont think its much.

How many times a week do you take tirz and what dose ??

 

[Juggy3838]

I’ve used semaglutide with my mother 70yrs old, who was pre diabetic. Added 80g protein to her diet, and bought her a blowflex. I don’t have the numbers from her last metabolic clinic visit, but A1C down, muscle mass up, bone mass up, fat mass down, and liver fat down.

Like @Mac11wildcat said….typical American, instead of eating 3,000 calories of absolute bullshit, they eat 1,000 calories of bullshit. If you had them eat 1,400 calories of micronutrient dense high protein food+ resistance training, I think we change the outcomes.

 

[Type-IIx]

Ozempic and Mounjaro are More Than Just Weight Loss Drugs: GLP-1 and GIP Agonists as Partitioning Agents

Recomp (↑LBM and ↓FM) and Incretins (e.g., GLP-1 and GIP agonists like Semaglutide, Tirzepatide) vs. Insulin (exogenous) – Partitioning (the p-ratio) –

thinksteroids.com

Boom! New article just landed (thanks @Millard). 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!

 

[Type-IIx]

Ozempic and Mounjaro are More Than Just Weight Loss Drugs: GLP-1 and GIP Agonists as Partitioning Agents

Recomp (↑LBM and ↓FM) and Incretins (e.g., GLP-1 and GIP agonists like Semaglutide, Tirzepatide) vs. Insulin (exogenous) – Partitioning (the p-ratio) –

thinksteroids.com

Boom! New article just landed (thanks @Millard). 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. Distinguishing between insulin resistance & hyperglycemia (common bodybuilding misunderstandings of IR)
7. How exogenous insulin (slin) worsens insulin sensitivity despite ameliorating hyperglycemia.

 

[29trt]

Great read!
Now on to the questions
What is the relation between Glp1( specifically semaglutide) and heart rate? It seems to increase it in some individuals more than others( I got 10bpm more on 1mg/week)?

Isn't the increase in insulin production stimulated by sema/tirz counter productive to the insulin sensitising effects?

 

[Type-IIx]

Great read!
Now on to the questions
What is the relation between Glp1( specifically semaglutide) and heart rate? It seems to increase it in some individuals more than others( I got 10bpm more on 1mg/week)?

Isn't the increase in insulin production stimulated by sema/tirz counter productive to the insulin sensitising effects?

Semaglutide does not seem to have a significant effect on heart rate (discernible vs. placebo) as you say, at least according to recent meta-analytical data. Rather, tirzepatide dose-dependently increases HR due to an unknown mechanism, speculatively, perhaps due to GIP agonism per se, but still unelucidated.

 

[primojuju]

FDA Approves New Medication for Chronic Weight Management

The FDA approved Zepbound (tirzepatide) for chronic weight management in adults with obesity or are overweight.

www.fda.gov

fda said OK on tirz for weight loss, I was expecting a more silly drug name than "Zepbound".

 

[psauce]

This is a serious clinical problem, too. Most (not all) obese people live a sedentary lifestyle, and muscle is an expensive and metabolically active tissue. While it’s *great* that there is a drug that can reliably curb appetite without serious health problems, severe caloric restriction is identical to anorexia nervosa in its impact on the body — the single most lethal mental health pathology that we know of.

Resistance exercise is necessary on these drugs, not an optional lifestyle addition.

 

[Type-IIx]

This is a serious clinical problem, too. Most (not all) obese people live a sedentary lifestyle, and muscle is an expensive and metabolically active tissue. While it’s *great* that there is a drug that can reliably curb appetite without serious health problems, severe caloric restriction is identical to anorexia nervosa in its impact on the body — the single most lethal mental health pathology that we know of.

Resistance exercise is necessary on these drugs, not an optional lifestyle addition.

I've never looked into the matter, do you happen to know whether muscle loss, without these incretin drugs in sedentary T2DM patients, is typically more than ~50% or 1/2 after initiating starvation?

My initial thinking is – given the metabolic expense of skeletal muscle & considering "simplified" teleological factors like the "thrifty gene" hypothesis vis-à-vis T2DM patients; human evolution's being shaped by droughts, famines, starvation and the need for survival during periods of food scarcity; etc. – that frank starvation without any drug or resistance training intervention would probably result in greater than half of decreases from body tissues being from skeletal muscle. Immobilization in patients who are bed-bound for long hospital stays and the resulting changes in body tissues strikes me as being comparable.

Do you agree/disagree? Why?

 

[psauce]

I've never looked into the matter, do you happen to know whether muscle loss, without these incretin drugs in sedentary T2DM patients, is typically more than ~50% or 1/2 after initiating starvation?

My initial thinking is – given the metabolic expense of skeletal muscle & considering "simplified" teleological factors like the "thrifty gene" hypothesis vis-à-vis T2DM patients; human evolution's being shaped by droughts, famines, starvation and the need for survival during periods of food scarcity; etc. – that frank starvation without any drug or resistance training intervention would probably result in greater than half of decreases from body tissues being from skeletal muscle. Immobilization in patients who are bed-bound for long hospital stays and the resulting changes in body tissues strikes me as being comparable.

Do you agree/disagree? Why?

That’s the million dollar question, and (IMO) the correct perspective on these meds.

For a patient with untreated T2DM, essentially every trajectory is worse than being treated with these drugs. Particularly the ones grabbing headlines now — muscle wasting and gastroparesis.

Being treated while you still have enough beta cells to produce insulin is infinitely better than progressing to t3 and requiring exogenous insulin. And we’re seeing that the heart disease, immobility, and other conditions that come with severe or morbid obesity are preventable with this intervention. Once those things happen from untreated T2DM, there’s really nothing to do but treat newly acquired symptoms and diseases.

By contrast, a patient can lower his or her dose to abate symptoms and pump the brakes on weight loss. Compared to other T2DM treatment options, it’s a game changer. It’s a really game changer.

Patients with obesity and T2DM who we see actually losing weight (which is rare, because it’s difficult) are regularly counseled on the importance of resistance training. If they’re seeing an endocrinologist or someone who specializes in metabolic diseases… those folks know the process. With people doing this minimally supervised or with a provider who may not have seen rapid weight loss, especially mid-levels who didn’t train in this area, it can be very scary. Drastic weight loss — either super rapid while still obese or to 14ish BMI — can really do a ton of organ damage, including skeletal muscle, hair, and teeth as well as all the squishy ones. The worst position to be in is simultaneously obese and malnourished, because the body can’t support the stresses of the overweight.

All told, these drugs are going to save a ton of lives. Some decent patient education and a very minimal weight lifting program paired with these drugs will make that process as harmless as possible.

 

[HB_22]

What is the relation between Glp1( specifically semaglutide) and heart rate? It seems to increase it in some individuals more than others( I got 10bpm more on 1mg/week)?

I had to stop semaglutide because of it, my rhr went from 63-65 to lower 70s. Sadly nebivolol didn’t help much.

 

[29trt]

I had to stop semaglutide because of it, my rhr went from 63-65 to lower 70s. Sadly nebivolol didn’t help much.

And it went back to normal after you stopped the sema?