Here is an article comparing the different weight loss medicines

[keangkong]

Here is an article comparing the different weight loss medicines: Ault, Retratrutide Produces Greatest Weight Loss (Jan. 7, 2025) Medscape. The article is based on another article, which I don't have although I'm attempting to get it: Moiz, et al. (2025). Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes. Annals of Internal Medicine. https://doi.org/10.7326/annals-24-01590. The greatest losses were seen with retatrutide, survodutide, and mazdutide.

Edit: I found the original article: Moiz, et al. (2025). Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes. Annals of Internal Medicine.

 

[brittmiche]

I believe it. What I don't understand is no appetite suppression with reta... But more loss

 

[hexagonal]

The glucagon receptor activity results in an increase to base metabolism.

But plenty of people experience appetite suppression with reta, just less of it than with some other glp1s.

 

[clayd]

tbh i am starting to wonder why i keep stocking up on tirz when reta is clearly superior for weight loss. maybe because it's getting cheaper. or maybe it's because i like the appetite suppression and the relative lack of side effects i experience.

 

[keangkong]

I believe it. What I don't understand is no appetite suppression with reta... But more loss

I have never taken reta although I own a vial and have a kit of 15 in transit. Reta increases your metabolism among other effects. I don't know you and haven't looked at your past posts. However, my guess is that you were taking another GLP-1 drug and tried reta. Comparatively, the reta is reducing your appetite less than the other drug. However, if reta is the only weight loss drug you've been on, then my theory is off. That's the danger of taking advice from a lawyer who lacks a medical/scientific background.

 

[Peevee]

tbh i am starting to wonder why i keep stocking up on tirz when reta is clearly superior for weight loss. maybe because it's getting cheaper. or maybe it's because i like the appetite suppression and the relative lack of side effects i experience.

I thought the same and stopped losing weight when I dropped the tirz. Everyone’s different though. So many people said they dropped weight super fast in Reta, I’m a bit disappointed
Edit I had great appetite suppression on 8mg Reta when I was not shitting my guts out. The suppression tapered off around day 5. Again, everyone’s different. 🤷‍♂️

 

[keangkong]

tbh i am starting to wonder why i keep stocking up on tirz when reta is clearly superior for weight loss. maybe because it's getting cheaper. or maybe it's because i like the appetite suppression and the relative lack of side effects i experience.

There is something to be said for staying on a medicine that's working well for you. Also, reta hasn't completed phase 3 trials.

 

[Peevee]

There is something to be said for staying on a medicine that's working well for you. Also, reta hasn't completed phase 3 trials.

I’m always chasing the next big thing. Don’t be me. I did it dieting and now I do it with peps. I’d be much better off if I just picked a plan and stuck with it

 

[clayd]

There is something to be said for staying on a medicine that's working well for you. Also, reta hasn't completed phase 3 trials.

It has been working for me but I'm approaching that final 20 pounds and expecting it's going to be tough to lose them, meanwhile I have 1000mg of tirz on hand and getting ready to order 800 more for some reason, I guess I'm just going to stay on max tirz forever during maintenance

 

[geoguy78]

tbh i am starting to wonder why i keep stocking up on tirz when reta is clearly superior for weight loss. maybe because it's getting cheaper. or maybe it's because i like the appetite suppression and the relative lack of side effects i experience.

There's the studies.... and then there's the real world. As we can see, on paper reta is better. But is it better in real life? I know people personally that switched to reta and it did not work for them, and they are back on tirz. I also know people that switched from sema to tirz, and tirz did not work for them. I like shiny new toys, but I've dropped approximately 50 pounds since the start of August on tirz. On paper reta is better, but the percentage that it is better is not significant enough for me to abandon what is obviously working extremely well when there's always the risk of setting myself back. By sticking with tirz, at the very worst I might hit my goal a month or two later than I would have had I started with reta. Like the saying goes, "if it ain't broke, don't fix it"

 

[geoguy78]

It has been working for me but I'm approaching that final 20 pounds and expecting it's going to be tough to lose them, meanwhile I have 1000mg of tirz on hand and getting ready to order 800 more for some reason, I guess I'm just going to stay on max tirz forever during maintenance

Just crank up the dose, unless the sides are bugging you, of course. Plenty of gray market users pinning well in excess of 15mg per month of tirz, and EL is currently testing 20 and 25mg doses.

 

[zpped]

I stopped 6mg of tirz and switched to 2.5mg of reta. 3 weeks of 2.5, then 4, and I'm still on 6mg. I didn't start losing weight on reta until my last week of 4mg.

I only lost a couple pounds in that time but much better body comp over all


A lot of people also dose too frequently with reta. It really does work better weekly.

 

[clayd]

Just crank up the dose, unless the sides are bugging you, of course. Plenty of gray market users pinning well in excess of 15mg per month of tirz, and EL is currently testing 20 and 25mg doses.

That's the plan. Crank the dose as far as I need to and add whatever other stackers I need

 

[nurseratchit]

I believe it. What I don't understand is no appetite suppression with reta... But more loss

There actually is but it's a lot more subtle and takes longer to kick in than sema or tirz. I definitely experienced more hunger and cravings while I was titrating up so it was a nail biter for a couple of weeks. At higher doses, reta effectively puts your body into a ketogenic state without having to be on a keto diet. The glucagon agnonism also increases BMR. I'm still only at 4mg at waiting for the experience of eating more while still losing weight that a lot of people report.

 

[hexagonal]

I stopped 6mg of tirz and switched to 2.5mg of reta. 3 weeks of 2.5, then 4, and I'm still on 6mg. I didn't start losing weight on reta until my last week of 4mg.

I only lost a couple pounds in that time but much better body comp over all
View attachment 5045

A lot of people also dose too frequently with reta. It really does work better weekly.

Plenty of people get great results dosing twice a week on reta.

For me the heart rate side effects are too high to do weekly, too.

 

[zpped]

Plenty of people get great results dosing twice a week on reta.

For me the heart rate side effects are too high to do weekly, too.

Just because it works, doesn't mean it wouldn't be working better if dosed properly. But twice a week is still way less than the people that are doing it everyday. Drug responses are not linear to the serum level. If the serum levels don't spike enough the ketogenic effects are lot likely to happen.

Heart rate increases more than 7-8 bpm are usually from titrating too quickly. But obviously any individual may just respond badly at any level.

 

[hexagonal]

Just because it works, doesn't mean it wouldn't be working better if dosed properly. But twice a week is still way less than the people that are doing it everyday. Drug responses are not linear to the serum level. If the serum levels don't spike enough the ketogenic effects are lot likely to happen.

Heart rate increases more than 7-8 bpm are usually from titrating too quickly. But obviously any individual may just respond badly at any level.

So... if you dose once a week and the ketogenic effects are only there at the start, then you don't get them for the rest of the week? By that logic you should be dosing more frequently at levels that keep it high enough to cause the ketogenic impact.

But the idea that ketogenic effects are a significant part of the weight loss is, to the best of my knowledge, all speculation at this point. I also just grabbed a ketone test strip and tested, and yep, still ketones, despite this being before injection on an injection day for me.

All we can definitively say is that the trials are based on weekly injections and show the results they show. The rest is speculation and assumptions.

 

[zpped]

So... if you dose once a week and the ketogenic effects are only there at the start, then you don't get them for the rest of the week? By that logic you should be dosing more frequently at levels that keep it high enough to cause the ketogenic impact.

But the idea that ketogenic effects are a significant part of the weight loss is, to the best of my knowledge, all speculation at this point. I also just grabbed a ketone test strip and tested, and yep, still ketones, despite this being before injection on an injection day for me.

All we can definitively say is that the trials are based on weekly injections and show the results they show. The rest is speculation and assumptions.

Like I said, it's more of issue for the people that are taking it everyday. No one is coming to arrest you injecting it twice a week. But there are lots of reasons for the way the dosing schedule was designed. I'm relaying the opinions of medical professionals that have been participating in the actual reta trial. Why it works better that way is definitely speculation, but its not speculation that it works better that way for the majority of people.

 

[hexagonal]

Like I said, it's more of issue for the people that are taking it everyday. No one is coming to arrest you injecting it twice a week. But there are lots of reasons for the way the dosing schedule was designed. I'm relaying the opinions of medical professionals that have been participating in the actual reta trial. Why it works better that way is definitely speculation, but its not speculation that it works better that way for the majority of people.

I've not seen anything like that in any of the papers on the reta trials that I have read. Can you link them?

 

[zpped]

I've not seen anything like that in any of the papers on the reta trials that I have read. Can you link them?

There aren't papers on their opinions. Go to the roundtable and you can read them for yourself.

 

[hexagonal]

There aren't papers on their opinions. Go to the roundtable and you can read them for yourself.

So what you're saying is you can't link anything?

And anecdotal opinions aren't worth much. In god we trust, all other must provide data.

 

[zpped]

So what you're saying is you can't link anything?

And anecdotal opinions aren't worth much. In god we trust, all other must provide data.

Nope can't link it because it's long in depth conversations. I could link all the actual studies done on reta but you already know that they all use weekly dosing and I doubt it matters to you because you think you know why even though it's complete speculation.

How about you put up something to prove your theory about split dosing since it goes against the actual studies?

 

[hexagonal]

Nope can't link it because it's long in depth conversations. I could link all the actual studies done on reta but you already know that they all use weekly dosing and I doubt it matters to you because you think you know why even though it's complete speculation.

How about you put up something to prove your theory about split dosing since it goes against the actual studies?

I'm not the one making strong claims about the efficacy of weekly dosing vs. more frequent.

But we can look at what we know in other medications and extrapolate from there.

We tend to find more frequent dosing performs as well as longer dosing, and sometimes better:

https://academic.oup.com/eurheartj/article-abstract/38/suppl_1/ehx501.81/4087668?redirectedFrom=fulltext&login=false

Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis - Cardiovascular Drugs and Therapy

Purpose We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing of statins. Methods We searched selected databases through January 2, 2017 to identify relevant RCTs and quasi-RCTs...

link.springer.com

Also something in common with peptides and GH: (To be fair, this is looking at daily injection of HGH vs. a modified form mean to have a longer half-life)

https://academic.oup.com/jcem/article/102/5/1578/2965085

We also know that a big part of why longer dosing is often preferred is adherence, e.g.

https://www.mayoclinicproceedings.org/article/S0025-6196(11)61559-0/abstract

Not to say that more frequent dosing is always better on every front - with TRT people often do it for a variety of reasons, but increased frequency has shown some risk when it comes to blood thickening:

https://academic.oup.com/jsm/article-abstract/13/Supplement_1/S18/7003555

From an empiricist perspective, we do not have data to speak strongly one way or the other. So I won't. From a rationalist perspective, we have plenty of data that overall serum levels tends to be what is important for medication efficacy, and no specific reason to believe retatrutide will behave any differently.

Are you wrong? I don't know - there is very little I would say I am confident that I know on any drug undergoing clinical trials. But I will say until provided reason to believe otherwise, my default assumption is to go with what is most likely from a statistical perspective - and that's that dosing frequency tends to have minor impact when total amount is proportional.

 

[keangkong]

But twice a week is still way less than the people that are doing it everyday. Drug responses are not linear to the serum level. If the serum levels don't spike enough the ketogenic effects are lot likely to happen.

The studies looked at once per week dosing. To my knowledge, and there are certainly many studies I didn't read on reta, reta has only been studied with once per week dosing. Deciding to only take it once per week since that's how it's been studied sounds like a reasonable decision, although I'll confess I take tirzepatide twice per week even though it too has only tested in trials once per week. As to your suggestion that you won't go into ketosis unless you take reta only once per week, I'm unaware of scientific basis for such a statement. If the drug makers thought taking reta once per week resulted in ketosis, they likely would have tried more frequent dosing to avoid causing diabetics to suffer from ketoacidosis.

 

[keangkong]

There aren't papers on their opinions. Go to the roundtable and you can read them for yourself.

I can't go to the round table. King Arthur wants to kill me because I slept with Guinevere.

 

[Laxfinity]

I believe it. What I don't understand is no appetite suppression with reta... But more loss

How does that even happen?

 

[zpped]

I'm not the one making strong claims about the efficacy of weekly dosing vs. more frequent.

You are making a claim that twice a week is as effective. Extrapolating is no less speculation. Statins are a very different class of drugs that work in a different way.

You're pretending that you're being more scientific than just following the studies and the subject experts that have weighed in on them (that you haven't bothered to go read).

 

[zpped]

The studies looked at once per week dosing. To my knowledge, and there are certainly many studies I didn't read on reta, reta has only been studied with once per week dosing. Deciding to only take it once per week since that's how it's been studied sounds like a reasonable decision, although I'll confess I take tirzepatide twice per week even though it too has only tested in trials once per week. As to your suggestion that you won't go into ketosis unless you take reta only once per week, I'm unaware of scientific basis for such a statement. If the drug makers thought taking reta once per week resulted in ketosis, they likely would have tried more frequent dosing to avoid causing diabetics to suffer from ketoacidosis.

It's a minor ketosis anyways. It's just an example of one thing that could explain why proper spacing between doses works better.

Heres the chart for tirz because it's what I've got on hand to show the non-linear response of these drug levels to receptor activation.

https://www.researchgate.net/figure/Tirzepatide-TZP-is-an-imbalanced-agonist-of-the-GIP-and-GLP-1-receptors-and-shows_fig1_343327974

If you want more details you're gonna have to make up with Arthur.

 

[hexagonal]

You are making a claim that twice a week is as effective. Extrapolating is no less speculation. Statins are a very different class of drugs that work in a different way.

You're pretending that you're being more scientific than just following the studies and the subject experts that have weighed in on them (that you haven't bothered to go read).

I am making a claim that we have no specific reason to believe that twice a week is less effective than once a week. For someone who is passing judgment on people's adherence to scientific principles, you should probably remember that the null hypothesis is a foundational part to science.

At current your argument is "Go read some anecdotal opinions buried somewhere in this thing that I won't link you to."

Even your latest link shows only a minor deviation from a linear response for a handful of hours before it returns to being linear. And if you plotted a second dosage, you'd see another spike bringing it back above the weekly dosing line. But you believe that a few hours out of the whole week is making a significant difference in the efficacy? If we have data where a disproportionate amount of weight is lost during that time period or we can see lasting downstream effects caused by the larger spike and those make sense from a mechanistic purpose, then sure, you might be on to something.

But instead your argument is that it might maybe be important for causing "minor ketosis," despite having provided no evidence that the effects on ketosis differ from one dosing schedule to another.

 

[zpped]

But instead your argument is that it might maybe be important for causing "minor ketosis," despite having provided no evidence that the effects on ketosis differ from one dosing schedule to another.

I'm not making an argument. And I'm definitely not wasting any more time on you.

Keep doing what ever you want. I was never trying to stop you.