I'm not impressed.

[Retazempic]

There’s a table floating around on this site and elsewhere. Looking for it now.

 

[Calm Logic]

Anyone trial >12 mg Reta or stalled on high dose reta?

Hey all, For some background, I've been on GLPs for >1.5 yrs. Started on Tirz, maxed out and stalled at 15mg. Switched to reta about 3 months ago and am currently at Reta 10mg. On my switch I regained about 10 lbs but reduced 3 of those lbs on reta so far. So net -7 lbs. Just wondering how...

glp1forum.com

 

[Retazempic]

Anyone trial >12 mg Reta or stalled on high dose reta?

Hey all, For some background, I've been on GLPs for >1.5 yrs. Started on Tirz, maxed out and stalled at 15mg. Switched to reta about 3 months ago and am currently at Reta 10mg. On my switch I regained about 10 lbs but reduced 3 of those lbs on reta so far. So net -7 lbs. Just wondering how...

glp1forum.com

That’s exactly it. Thanks!!

 

[CNCCurrency]

That’s exactly it. Thanks!!

Thats not proof on switching from one to other and how to dose for it, that I see.

 

[lessthanhalf]

Can anyone recommend a Reta starting dose coming from 15mg zepbound?

There are no official dose equivalents for the GLP's.

The answer depends a bit on what side effects you got from tirzepatide either at your current dose or as you increased doses. Obviously the more side effects the lower swapover dose. If you have cardiovascular disease maybe go lower as well due to the heart rate increase being larger on reta. And it depends on general health and other illnesses, especially diabetes.

In terms of straight equivalents it is probably about 8-10mg. Reta has higher glp-1 agonism and less gip agonism so can cause more gi side effects than tirz.

To be safeish I would go with 6-8mg, but there is always a chance of more side effects than expected from different GLP's, so if being a bit pukey for a week might interfere with work or something else go lower rather than higher.

 

[CNCCurrency]

There are no official dose equivalents for the GLP's.

The answer depends a bit on what side effects you got from tirzepatide either at your current dose or as you increased doses. Obviously the more side effects the lower swapover dose. If you have cardiovascular disease maybe go lower as well due to the heart rate increase being larger on reta. And it depends on general health and other illnesses, especially diabetes.

In terms of straight equivalents it is probably about 8-10mg. Reta has higher glp-1 agonism and less gip agonism so can cause more gi side effects than tirz.

To be safeish I would go with 6-8mg, but there is always a chance of more side effects than expected from different GLP's, so if being a bit pukey for a week might interfere with work or something else go lower rather than higher.

I guess, put all this advice not based on science in a hat shake it up and draw one and help for the best?

 

[Retazempic]

All that science is occurring in this site

 

[CNCCurrency]

All that science is occurring in this site

 

[tubby]

I would think they are just too different to do that

I mean that's exactly what the Reta-zempic guy would try to tell you. You're going to need to hit up Retazepatide if you want a straight answer to your question, I'm afraid.

 

[lessthanhalf]

I guess, put all this advice not based on science in a hat shake it up and draw one and help for the best?

I think my estimates and guesses were soundly based on the science.

 

[CNCCurrency]

I think my estimates and guesses were soundly based on the science.

Whose?

 

[CNCCurrency]

I mean that's exactly what the Reta-zempic guy would try to tell you. You're going to need to hit up Retazepatide if you want a straight answer to your question, I'm afraid.

When you have no degree or specialty in these non science base options on changing from one glp1 to another, means jack shit. So am I supposed to believe you are the expert in any of these protocals





?

 

[Fishcakes88]

There are no official dose equivalents for the GLP's.

The answer depends a bit on what side effects you got from tirzepatide either at your current dose or as you increased doses. Obviously the more side effects the lower swapover dose. If you have cardiovascular disease maybe go lower as well due to the heart rate increase being larger on reta. And it depends on general health and other illnesses, especially diabetes.

In terms of straight equivalents it is probably about 8-10mg. Reta has higher glp-1 agonism and less gip agonism so can cause more gi side effects than tirz.

To be safeish I would go with 6-8mg, but there is always a chance of more side effects than expected from different GLP's, so if being a bit pukey for a week might interfere with work or something else go lower rather than higher.

Hi, I saw on youtube and read some post on sites, they mentioned Reta has more GIP and less GLP, while Tirz is the opposite.

Just wanting to clarify. Thanks.

 

[Retazempic]

But my username’s Retazempic. That has to count for something.

 

[lessthanhalf]

Whose?

I do not claim to be a genuine expert , but I do have a related degree, and have read pretty much every glp-1 related paper I have found over several years, spending at least a few hundred hours on research, so I think my statement is entirely reasonable. My guesses and estimates are based on a reasonably thorough understanding of the science.

 

[CNCCurrency]

Yes, I understand that. that's why I waited until week 3 as I was on a preclinical dose to get the feel of it and made the decision to move up to a more typical starting dose of .25. I appreciate the input.

 

[lessthanhalf]

Hi, I saw on youtube and read some post on sites, they mentioned Reta has more GIP and less GLP, while Tirz is the opposite.

Just wanting to clarify. Thanks.

I have done this about 3 times now, but.

All the receptors activation contribute to the appetite supressing and weight loss effects of the different glp's. GLP-1, GIP and Glucagon - all agonists

The behaviour of these drugs at glp-1 receptors is complex. 99% of the drug is bound to albumin to start with which influences how much is available at the receptors. Most of the ki or binding affinity numbers online are not necessarily correct, and AI responses are not either, and most of the info is buried in early studies usually under the drug development names which are different. I spent a fair bit of time trying to work this out after seeing different and contradictory information about the activity of different GLP's on the receptors, so I think my information is correct but cannot be certain. I did dig through quite a few papers to work this out.

The effect of the drugs after binding to the receptors is via secondary intracellular messengers, for glp-1 beta-arrestin and cAMP it is these that determine the effects. Tirzepatide has intentionally designed biased agonism on glp-1 affecting beta-arrestin less than natural glp or semaglutide or retatrutide. Beta arrestin once activated causes the glp-1 receptors to be taken inside the cell so they can no longer have an effect. This is how a dosage adjusted amount of tirzepatide can have a stronger effect on glp-1 than semaglutide, despite lower affinity. And it also leads to less nausea although I am not sure by what mechanism. Glp-1 agonism causes nausea and malaise and food aversion responses.

Gip agonism is not as complicated, but from what I could determine tirzepatide has stronger effects than retatrutide. Gip agonism counteracts nausea and malaise and food aversion due to glp-1 responses via brain receptors. Tirzepatides stronger gip agonism is mainly why it causes less gi side effects.

so in terms of glp-1 effects on weight loss it is probably tirzepatide>semaglutide>retatrutide ( assuming standard maximum doses )

Despite this semaglutide and retatrutide have stronger binding to glp-1 than tirzepatide, but the total effect after the biased signalling is taken into account changes this.

In terms of gi adverse effects ( glp-1 adverse effects ) semaglutide>retatrutide>tirzepatide

retatrutide has better weight loss due to the added glucagon agonism, but is more likely to increase heart rate, and probably more likely to cause skin sensory symptoms. I have attempted to work this out without sucess. The high dose semaglutide study showed high rates of skin sensory symotoms, but were rare in the low dose studies, so it has to be via glp-1, but does not explain why it is more common from reta.

Tirzepatide has less gi side effects than semaglutide and retatrutide mainly due to the stronger gip agonism counteracting the effects of glp agonism on nausea.

Not exactly crystal clear explanation, but I think this view of the receptor effects fits with the different side effect profiles of the different glp's fairly well.

 

[Fishcakes88]

I have done this about 3 times now, but.

All the receptors activation contribute to the appetite supressing and weight loss effects of the different glp's. GLP-1, GIP and Glucagon - all agonists

The behaviour of these drugs at glp-1 receptors is complex. 99% of the drug is bound to albumin to start with which influences how much is available at the receptors. Most of the ki or binding affinity numbers online are not necessarily correct, and AI responses are not either, and most of the info is buried in early studies usually under the drug development names which are different. I spent a fair bit of time trying to work this out after seeing different and contradictory information about the activity of different GLP's on the receptors, so I think my information is correct but cannot be certain. I did dig through quite a few papers to work this out.

The effect of the drugs after binding to the receptors is via secondary intracellular messengers, for glp-1 beta-arrestin and cAMP it is these that determine the effects. Tirzepatide has intentionally designed biased agonism on glp-1 affecting beta-arrestin less than natural glp or semaglutide or retatrutide. Beta arrestin once activated causes the glp-1 receptors to be taken inside the cell so they can no longer have an effect. This is how a dosage adjusted amount of tirzepatide can have a stronger effect on glp-1 than semaglutide, despite lower affinity. And it also leads to less nausea although I am not sure by what mechanism. Glp-1 agonism causes nausea and malaise and food aversion responses.

Gip agonism is not as complicated, but from what I could determine tirzepatide has stronger effects than retatrutide. Gip agonism counteracts nausea and malaise and food aversion due to glp-1 responses via brain receptors. Tirzepatides stronger gip agonism is mainly why it causes less gi side effects.

so in terms of glp-1 effects on weight loss it is probably tirzepatide>semaglutide>retatrutide ( assuming standard maximum doses )

Despite this semaglutide and retatrutide have stronger binding to glp-1 than tirzepatide, but the total effect after the biased signalling is taken into account changes this.

In terms of gi adverse effects ( glp-1 adverse effects ) semaglutide>retatrutide>tirzepatide

retatrutide has better weight loss due to the added glucagon agonism, but is more likely to increase heart rate, and probably more likely to cause skin sensory symptoms. I have attempted to work this out without sucess. The high dose semaglutide study showed high rates of skin sensory symotoms, but were rare in the low dose studies, so it has to be via glp-1, but does not explain why it is more common from reta.

Tirzepatide has less gi side effects than semaglutide and retatrutide mainly due to the stronger gip agonism counteracting the effects of glp agonism on nausea.

Not exactly crystal clear explanation, but I think this view of the receptor effects fits with the different side effect profiles of the different glp's fairly well.

Thank You for your explanation, I do appreciate the reply.

 

[tubby]

I do not claim to be a genuine expert , but I do have a related degree, and have read pretty much every glp-1 related paper I have found over several years, spending at least a few hundred hours on research, so I think my statement is entirely reasonable. My guesses and estimates are based on a reasonably thorough understanding of the science.

I suspect they're just teasing you for referring to "the science," which has become a very common form of the "appeal to authority" logical fallacy in the current decade. I'm not accusing you of doing this, but it's become quite fashionable for a random reporter or internet influencer to invoke "the science" as their means of spitting out an answer without being capable of actually justifying that answer. It's kind of the modern version of what in the 1960s would have been "because my dad says it's that way."

I know that's not what you meant when you said it (and you generally seem to be informed on the topics you discuss). I'm just telling you how it comes across to most people who hear "the science."

 

[CNCCurrency]

I do not claim to be a genuine expert , but I do have a related degree, and have read pretty much every glp-1 related paper I have found over several years, spending at least a few hundred hours on research, so I think my statement is entirely reasonable. My guesses and estimates are based on a reasonably thorough understanding of the science.