Tirzepatide - a better semaglutide? (GIP + GLP1 agonism). Also LY3437943

If I’m going to speculate, it’s the same side effect that he prominently talked about as with rapamycin, coincidence? Hasn’t he detected any side effects from the few dozen pills (~100 interventions?), he does?

Optimizing certain biomarkers without knowing the causal pathway seems a bit low tier and not something you, to be honest, expect from someone who has a team and is dedicated to it as well. The mechanism of action matters as well. Otherwise it’s Goodhart’s law. It’s like optimizing grip strength because people who are frail and score low have increased mortality. So that doesn’t make you immortal because you keep increasing your strength because a bunch of people scored low & had increased mortality. Or they are using studies done on like 50 year olds, where a certain marker had a “decrease in all cause mortality”, but it’s about useless as it isn’t max lifespan, and the base rate is so low so the absolute risk is a rounding error. That’s the same thing with the VO2 Max study here: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2707428 they did in in 53 year old with LOW BASE RATE mortality. It says little of maximum lifespan over a lifetime.

My point is I think you need to know HOW resting heart rate improves or increases mortality. Then you need to see if your intervention does it via that mechanism of action and actually see what the difference is on LIFETIME risk.

The sleep trackers like whoop isn’t totally accurate either. I’ve felt like I’ve had great sleep but the scores are low, it’s just dumb, it would be better with something that measures brainwaves.

I’m just a layman so I don’t know. Peter Attia loved that VO2 Max study.

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He only finds side effects for prescription meds he can’t sell. :slight_smile:

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This makes his protocols less potent. It’s back to eat well, exercise, sleep and don’t hurt your body. This will get you to 92 and maybe 100, but he will eventually die before 115.

You need prescription drugs like Rapamycin in order to break longevity records. Supplements, common sense and hard work only go so far albeit you need them as well. It’s like building a building with only a solid foundation. You need to use modern technology (prescription drugs) if you want the Burj Khalifa.

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My sleep apnea resolved after using GLP1s. It also helps that I lost 150 lbs. So better sleep quality for me.

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Just to clarify some of the comments here, are people actually getting peptide powders from non-pharmacy providers and reconstituting?

This makes my hair stand up because I seriously damaged my health dabbling in this some years ago. Ended up in the hospital for a few days, took 6 months to be functional again. Not conclusive but likely endotoxins in one of the vials.

Anyhow, be very extra careful when you bypass the liver. Obviously it’s fine most of the time but when it goes badly, it goes really badly.

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That is a helpful PSA.

Are you comfortable sharing where you sourced your peptide? You can PM me if not wanting to broadcast it because you can’t be 100% sure. Thx

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On Bryan Johnsons sleep score impacts from Triz, I think he means in terms of amount of deep sleep, amount of REM and number of sleep disruptions. I use the Apple watch and Athlytic app which is kinda like Whoop for Apple Watch. It rates my sleep score based on a number of factors including do I met at least 33% of the total time in Deep+REM, number of sleep disruptions (times you wake at night), total sleep time and sleep latency. I think it could be possible that Triz will impact one of those metrics. It seems BJ is very focused on the amount of deep sleep time which just for me personally I did see an impact with Triz as well. I think this is just transitory and corrects after 3-6 months just like RHR increases.

Most members of this forum are experimenting with off label use of a variety of molecules. Which peptide did you use and where was it sourced?

Sure thing, I’m not entirely sure the source still exists today. This was in 2018 and it was called X-peptides. If I remember correctly, they did not have a much of a website and operated mostly on forums. It’s kind of a generic name and while there seem to be other stores up with that name now i couldn’t say whether they are actually the same. I used bpc-157 and ipamorelin.

This was at a time where I was operating at full Dunning-Kruger capacity and thought I knew a lot when I really didn’t.

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I think he’s using the Oura ring sleep score here… Your Oura Sleep Score & How To Interpret It

Bryan Johnson mentioned in 2019 he was using the Oura ring, but I’m not sure if that still the case: Bryan Johnson

And while I don’t know if 10% over a 3 week period is a long enough trial in this scenario, we do know that sleep is important.

Right now I’m wondering about the impact of SGLT2 inhibitors; it definitely increases the need to urinate at night, thus can interrupt sleep (but I need to try more hydration towards morning, and avoid in the afternoon evening). But if an SGLT2 drug causes you to wake up once or twice during the night, you have to wonder if the trade-off on sleep quality is worth it long term. I don’t have a Whoop or sleep tracking ring right now, so at some point I may get more detailed impact data.

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I don’t believe he’s still using the oura. For the past several years he has referred to and posted screenshots of his sleep performance from the whoop. Do you have a more recent reference to his Oura usage?

https://x.com/bryan_johnson/status/1682516773978148869?s=46

He has several posts on X where he mentions he uses whoop and not the Oura. Search Oura on his page to see.

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Not sure how relevant this may be to anyone here, this is in frank diabetics with a lot of risk factors, but here goes:

Eye Complications Found With Use of Semaglutide, Tirzepatide

https://www.medscape.com/viewarticle/eye-complications-found-use-semaglutide-tirzepatide-2025a100032f?form=fpf

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“The researchers hypothesized that rapid correction of hyperglycemia induced by these drugs, rather than direct toxicity of the medications, could be associated with the reported ophthalmic complications”

So yeah, probably not relevant for non-diabetics. But, it certainly seems to argue for caution against too rapid of an improvement if one is diabetic, potentially starting at an even lower dose and going slower with dose increases than standard dosing protocols.

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Interesting paper. Apparently tirzepatide NOT retatrutide has so far shown the best lean mass-preserving effect with weight loss:

https://www.metabolismjournal.com/article/S0026-0495(24)00285-3/fulltext

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It’s going to be really difficult for future medications to beat tirzepatide.

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I can’t wait until they work on one that also targets lowering apob. The highest doses of reta already show a 20 to 30% decrease in ldl, along with many other benefits.

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Can you share the study you’re referring to? Is that independent of weight loss?

Healthcare utilization, mortality, and cardiovascular events following GLP1-RA initiation in chronic kidney disease

https://www.nature.com/articles/s41467-024-54009-3

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That’s good news! While I don’t seem to have experienced muscle loss using Rt and I’ve seen a few younger (40’s and 50’s) gym rats using Rt to trim the last few pounds to get ripped AND gain muscle at the same time, those are most likely not good examples.

I also noticed this in the article.

Emerging activin/myostatin inhibitors may preserve lean mass during weight loss while promoting fat reduction leading to quality weight loss.

The newest activin agonist is cagrilintide developed by Novo to improve semaglutide weight loss performance, in response to Eli eating their lunch on weight loss performance with Tz.

This is the reason I’ve been testing Follistatin 344 to see if that might increase muscle or prevent muscle loss as it is a myostatin inhibitor. Been taking 100mcg daily for 3 weeks now. I stopped resistance training in Oct, due to laziness, so that fit in with my test plan LoL!

I have noticed that my biceps and tricepts seem to be a bit more “full” the last couple times I’ve flexed in the mirror. They are not quite as firm as they were the end of Sept but they are definitely not any smaller (thankfully :slight_smile: )

I mentioned else where that I had a little challenge from a friend who didn’t believe I could do 25 push ups. First 20 were pretty easy, the last 5 much harder. So even with no resistance training for 4 months I am still doing OK strength wise. Still can stand on one foot, either one, for over 2 minutes but my grip strength is not as good as I’d hoped. Picked up a grip dyno a month ago just to keep track of this one.

With 18 months on GLP1-R’s (Tz to Rt), things are still going well.

With this new info on muscle loss, I think we will transition back to Tz over the next 3 weeks.

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