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

 

[Type-IIx]

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

Did you happen to initiate or titrate up dose of rhGH at the same time?

I ask because there is robust data that in aged men, 1.8 IU q.d. rhGH s.c. increased RHR by precisely this degree: by 7.3 ± 1.9 beat/min.

For about the first week after initiating rhGH or titrating up dose the RAAS is ramped up. It can be reversed by Ibuprofen.

 

[M@NU]

Did you happen to initiate or titrate up dose of rhGH at the same time?

I ask because there is robust data that in aged men, 1.8 IU q.d. rhGH s.c. increased RHR by precisely this degree: by 7.3 ± 1.9 beat/min.

For about the first week after initiating rhGH or titrating up dose the RAAS is ramped up. It can be reversed by Ibuprofen.

i am on hgh since 2018 non stop and everytime introducing semaglutide, my RHR jumps up around 8-9 points.
Tirzepatide does not do this (atleast not notable).
So for me atleast, it is independent of the increase that comes with HGH.

 

[Type-IIx]

i am on hgh since 2018 non stop and everytime introducing semaglutide, my RHR jumps up around 8-9 points.
Tirzepatide does not do this (atleast not notable).
So for me atleast, it is independent of the increase that comes with HGH.

Strange. The literature describes this occurring for tirzepatide but not semaglutide at present.

I believe you. It's just that the prevalence is unknown. The most recent pamphlet from Wegovy that I've seen lists sinus tachycardia as a moderate side effect, the prevalence being unknown, but its onset rapid.

This data must come from post-marketing information (user reports after the drug starts being sold). It was not detected in any of the multicenter randomized controlled trials for semaglutide.

 

[M@NU]

Strange. The literature describes this occurring for tirzepatide but not semaglutide at present.

I believe you. It's just that the prevalence is unknown. The most recent pamphlet from Wegovy that I've seen lists sinus tachycardia as a moderate side effect, the prevalence being unknown, but its onset rapid.

This data must come from post-marketing information (user reports after the drug starts being sold). It was not detected in any of the multicenter randomized controlled trials for semaglutide.

strange that its inverse for me in regards to Tirz vs sema
but they are plenty of logs reporting RHR increase on semaglutide. Reddit (i think this is the place with most GLP-1 agonist users) has many posts with similar reactions.
I guess most "regular folks" user might not even realize if there RHR increases by 5-10 points since the general population gives a fuck about it. And those who are obese probably have a RHR of 90+ anyway so the inrease might be lower than 8-9 points

 

[Isrrike]

strange that its inverse for me in regards to Tirz vs sema
but they are plenty of logs reporting RHR increase on semaglutide. Reddit (i think this is the place with most GLP-1 agonist users) has many posts with similar reactions.
I guess most "regular folks" user might not even realize if there RHR increases by 5-10 points since the general population gives a fuck about it. And those who are obese probably have a RHR of 90+ anyway so the inrease might be lower than 8-9 points

Yes I’m on 4iu nordi and .5mg sema my rhr has gone up by about 10-15. I also notice getting up and doing any activity as small as walking to the fridge makes my hr 100

 

[HB_22]

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

Yes, that's right. It took some time, weeks, but that was probably due to the drug leaving the system.

Did you happen to initiate or titrate up dose of rhGH at the same time?

I ask because there is robust data that in aged men, 1.8 IU q.d. rhGH s.c. increased RHR by precisely this degree: by 7.3 ± 1.9 beat/min.

For about the first week after initiating rhGH or titrating up dose the RAAS is ramped up. It can be reversed by Ibuprofen.

Yes but I take hgh year around. My rhr of 63-65 is with hgh.

i am on hgh since 2018 non stop and everytime introducing semaglutide, my RHR jumps up around 8-9 points.

Same.

 

[Type-IIx]

Yes, that's right. It took some time, weeks, but that was probably due to the drug gettijg

Clearly a drug effect so. It's in their latest pamphlet (sinus tachycardia - moderate severity - acute onset - prevalence unknown), not sure if it was in their earlier ones. It must come from post-marketing reports (users reporting symptoms after the product is being sold).

 

[Isrrike]

Clearly a drug effect so. It's in their latest pamphlet (sinus tachycardia - moderate severity - acute onset - prevalence unknown), not sure if it was in their earlier ones. It must come from post-marketing reports (users reporting symptoms after the product is being sold).

Is it something concerning? My bp is stable at 100/60. Maybe from the slower gastric emptying our hearts are using more energy trying to digest?

 

[Type-IIx]

Is it something concerning? My bp is stable at 100/60. Maybe from the slower gastric emptying our hearts are using more energy trying to digest?

I'd be concerned if my RHR/pulse increased above 100 bpm. I'd stop using what was causing it.

I can't even begin to hypothesize about the mechanism. It could be a direct drug effect: GLP-1 may function to increase the rate of SA impulse during pacemaking, or something else may cause the same result.

I wouldn't think it's a byproduct of any benefit of the drug, related, e.g., to delayed gastric emptying.

 

[clearheaded]

I wonder if its something to do with "shunting" of blood to your guts when you digest.. ie colder hands feet but increase heart rate after food... something in and around that mechanism (or drug action not related to slowing of emptying per say) perhaps.

 

[bilbobagginz101]

I believe you. It's just that the prevalence is unknown. The most recent pamphlet from Wegovy that I've seen lists sinus tachycardia as a moderate side effect, the prevalence being unknown, but its onset rapid.

I can also corroborate this effect. My RHR goes up similarly on Sem, and all of my HR zones get a bit outta whack.

 

[DanishPanther]

Because it's handed out clinically by real doctors without diet or training recommendations ... they don't give a damn about muscle mass it seems, and neither does Novo Nordic.

All you have to do is increase your protein intake obviously, and you won't lose much muscle mass. esp if you lift as well - just like with a real diet, the bigger the deficit and the leaner you are, the more it always takes to hold onto your muscle mass.

But this is a med that is subscribed to millions of people, who would not or could not, follow diet or training advice ... and it still works!

It works mostly by minimizing your appetite.

A famous coach in our community has had many of these clients on semaglutide and a diet close to Lyles RFL, and his clients do not lose significant amounts of muscle mass.

 

[clearheaded]

Because it's handed out clinically by real doctors without diet or training recommendations ... they don't give a damn about muscle mass it seems, and neither does Novo Nordic.

thats simply not true... every dr will say to diabetic or someone trying to loose weight to obv eat less and move more.. they can only say so much and folks in USA are SOOO free they dont like Drs telling them not to drink coke esp more than once... (and FYI USA is #15 freest country, up from 17 several years ago)

I dunno but even when in best shape in 20s, I was like dr I need something to sleep my insomnia has be in a daze and hard to function... said well how much cardio do u do... 30-40min 5 days a week... he was like well do more lol and prob drink less booze... as most of you guys know diet and excersise is cure for ALOT of ailments and nearly every DR has said this to me.

even Drs have said lift heavy weights if want more T...

the fact is people WANT pills... they dont want to be told to change lifestyle..Drs know this aswell they can say all they want about life-style 95% of people won't change anything no matter what u say. ie stop smoking stop eating candy etc etc.

 

[DanishPanther]

thats simply not true... every dr will say to diabetic or someone trying to loose weight to obv eat less and move more.. they can only say so much and folks in USA are SOOO free they dont like Drs telling them not to drink coke esp more than once... (and FYI USA is #15 freest country, up from 17 several years ago)

I dunno but even when in best shape in 20s, I was like dr I need something to sleep my insomnia has be in a daze and hard to function... said well how much cardio do u do... 30-40min 5 days a week... he was like well do more lol and prob drink less booze... as most of you guys know diet and excersise is cure for ALOT of ailments and nearly every DR has said this to me.

even Drs have said lift heavy weights if want more T...

the fact is people WANT pills... they dont want to be told to change lifestyle..Drs know this aswell they can say all they want about life-style 95% of people won't change anything no matter what u say. ie stop smoking stop eating candy etc etc.

Yes it is, I don’t know what whoever distributes them in the US does, but they are not developed in the US.

There is at least as many studies based on just giving the meds without any training or diet changes as there is with clinical nutrition and dieting.

Fun fact btw. people in the drug only groups do way better than people in the training and diet only group: but obviously those who do both do the best.

Some of the compounds actually conserve more muscle under the same kcal deficit size, they don’t burn more (unlike peds like t3), even though they both improve t4 production as well as t4 to t3 conversion,

The thing is that even in the studies with training and diet, the protein is low compared to what guys in here eat (0,8 grams or kg of body weight), and the training is not strength training.

Most normal people are unable to get themself to change their habits, lifestyle and such, that is fail ‘just diet, or just train’ - that is why this meds and diabetes 2 meds are profitable to begin with.

Anyone smart, is careful not to make a caricature out of those, just to boost their own ego.

None the less, it’s less likely to be a problem for guys in here.

 

[BigJ1]

New to alot of this.. but alot of the ozempic prescribed people that are obese, aren't working out. They are just taking tge doses and not doing much else. Someone like me on trt, working out 5 days a week probably wont lose muscle protein to such a degree. I suspect some will be, but certainly not that much.

 

[readalot]

Is it something concerning? My bp is stable at 100/60. Maybe from the slower gastric emptying our hearts are using more energy trying to digest?

Frontiers | Safety of Semaglutide

<p>The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and the only GLP-1RA currently ...

www.frontiersin.org

Several clinical mechanistic trials provided conflicting evidence while aiming to understand the GLP-1RA-induced heart rate-increase. Some studies found systemic vasodilation (with likely consequent reflex tachycardia), while others failed to show this (105–107). Similarly, discrepant findings are available for activation of the (cardiac) sympathetic nervous system (106, 108–111). Our own group previously hypothesized a direct effect of GLP-1RAs on sino-atrial cells (106), after exclusion of other potential causes. This postulation was later confirmed in a mouse model, where stimulation of GLP-1 receptors on atrial cells induced a chronotropic effect, but only when neuronal input was present (112).

 

[ShredSeason]

Wondering if a glp1 helps while using dnp to curb the appetite or if it’s detrimental

It helps on a massive scale. I was on both DNP and GH, the GLP kept my appetite absolutely nuked.

 

[Letits now]

I did weight training for years but slowly gained weight during that time to be about 60 pounds over normal bmi. And a large percentage of it was tub. I kind of got fed up and got some tirz. Some nausea the first two weeks and a ton of fatigue. Nausea went away but fatigue was present for the first two months. Started lifting again after about 3 weeks. Was incredibly weak. After 6 months and 60 pounds later my inbody scan said I lost about 45 pounds of fat and 15 pounds of muscle. Not ideal and I am just now getting back to pre-tirz weight training level but it’s definitely a part of it. Since I had so much to lose I am ok with the muscle loss but it’s definitely annoying.

 

[Night_Owl]

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

Looks interesting Millard on their website it has this chart about how downstream from APJ there will AMPK activation. Reminded me of how MOTS-c triggers the activation of AMPK, but this will likely be more effective.