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Devilseye

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I’ve been so disappointed by cagri. For one it activates calcitonin receptors that are present in the thyroid. Not ideal as calcitonin doesnt do anything for weight loss. Second, its affects are relatively short lived.

Some context first. Ive been on a combo of reta/sema (10mg/2mg because sema is covered by my insurance and reta is poor activator of GLP-1R too) and I stalled at about 30% weight loss. Ive been trying for two months to loose tge last ten pounds without success. I just kept stable at 30% flat. Cagri didnt do much difference either. Hunger curbed initially but effects didnt last it helped get me to 30% but then I took it out and no difference.

Enter eloralintide. Hunger curbed at initial 1mg dose significantly. Btw, 1mg was enough to loose my 10lbs. Even in clinical trials 1mg gave 10% bodyweight loss and 3mg barely gave better at about 12.5%. Only 9mg doubled the weight loss at 20% but ill never need that. Plus eloralintide doesnt activate calcitonin receptor. Its a winner for me.

All in all very happy with this trial. I just wish more distributors would have it accessible at their US/Canada warehouses. Id definitely buy. Right now i only see it on china warehouses.

Cheers!
 
Devilseye said:


I’ve been so disappointed by cagri.

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Congratulations on the 10lbs! It's fantastic that elora pushed you through the stall. I'm sure that's what EL is banking on.

Yeah, I was disappointed with cagri too. Didn't realize that it wasn't going to work for me until after I bought 5 kits. That was dumb.

What is your dose of tirzepatide and are you still taking the sema? I liked sema and probably should have just stacked with that.
 
Grogu said:


What is your dose of tirzepatide and are you still taking the sema? I liked sema and probably should have just stacked with that.

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I was on tirz a while back but switched to 10mg reta 2mg sema and sticking to that for maintenance. Reta is especially weak at activating GLP1R so they compliment each other. Probably what allowed me to get to 30%. Sema was my first one as itwas covered by insurance. Lost quickly about 12% bodyweight but then stalled for a while. Tirz 10mg with sema took me to about 25%. Reta pushed it further.

Sema is a good drug. It activates GLP1R miles and miles better than either tirz or reta. There is no comparing tirz or reta to sema for GLP1R. So adding even 1mg stacked with them makes biochemical sense. It will add at least 5% weight loss to either of them imo.
 
For reference, the EC50 of Semaglutide is virtually as potent as native GLP1 at activating GLP1R, that of tirzepatide is like 5-10 times lower and reta is like 100 times lower.

So yeah, they compliment for sure and probably improve even more glucose metrics.
 
Devilseye said:


I was on tirz a while back but switched to 10mg reta 2mg sema and sticking to that for maintenance. Reta is especially weak at activating GLP1R so they compliment each other. Probably what allowed me to get to 30%. Sema was my first one as itwas covered by insurance. Lost quickly about 12% bodyweight but then stalled for a while. Tirz 10mg with sema took me to about 25%. Reta pushed it further.

Sema is a good drug. It activates GLP1R miles and miles better than either tirz or reta. There is no comparing tirz or reta to sema for GLP1R. So adding even 1mg stacked with them makes biochemical sense. It will add at least 5% weight loss to either of them imo.

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Yeah, I really like sema too. And don't remember why I didn't continue to stack with that.

So, you're taking 10mg of reta 2mg of sema and 1mg of elora? Or did you just use the elora to get to goal and sticking with the reta/sema stack?
 
Grogu said:


So, you're taking 10mg of reta 2mg of sema and 1mg of elora? Or did you just use the elora to get to goal and sticking with the reta/sema stack?

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So yeah, im doing exactly that. 1mg elora, 10mg of reta and 2mg sema. I’m planning on finishing my current 10mg vial of elora and phasing it off and see if I can stick to reta/sema for maintenance. Well see. Too early to tell but ill report back in a month or two.
 
Devilseye said:


So yeah, im doing exactly that. 1mg elora, 10mg of reta and 2mg sema. I’m planning on finishing my current 10mg vial of elora and phasing it off and see if I can stick to reta/sema for maintenance. Well see. Too early to tell but ill report back in a month or two.

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Yes, if you would please update us, that would be fantastic.

Maybe I'll add a little sema to my stack🤔
 
I understand the thinking of adding sema to tirz or reta, sema is more potent on GLP-1 receptors. And I think there probably are situations where it makes sense, mainly if you do not get a lot of side effects from GLP-1 agonism, and it actually works in practice, reducing appetite without problems, but the receptor sensitivity or binding affinity is not the whole story, and it does not help that a lot of the numbers on the internet about this are not correct based on reading a stack of the original early papers and long discussions with chatgpt about it.

Sema is most potent on GLP-1, followed by reta then tirz, but tirz ( but not reta ) has biased affinity on GLP-1 so its maximal downstream effects on target cells is going to be larger than it would seem just from the binding affinity, and the dose is 5-10 higher, so it is really hard to say which activates glp-1 the most, it is definitely possible it is tirz, not sema or reta, once adjusted for doses, and accounting for the biased affinity.

The major reason tirz and reta have less GI side effects than sema is the GIP agonism , that counteracts some of the GLP-1 adverse effects, so for most people, most of the time they are better choices as they cause more weight loss and have less side effects. This is strongest for tirz and is likely the main reason it has the lowest side effect rates, as well as the effects of the biased agonism on GLP-1 reduce adverse effects as well, though the mechanism for this I find a bit confusing.

I would expect based on this that most people would be better off on higher dose of tirz or reta than lower doses with some sema added in, but if experimentation proves otherwise, I won't argue, GLP responses do seem pretty individual at times, no doubt there is a stack of receptor polymorphism in the incretin receptors and variation in the downstream pathways as well.
 
lessthanhalf said:


I understand the thinking of adding sema to tirz or reta, sema is more potent on GLP-1 receptors. And I think there probably are situations where it makes sense, mainly if you do not get a lot of side effects from GLP-1 agonism, and it actually works in practice, reducing appetite without problems, but the receptor sensitivity or binding affinity is not the whole story, and it does not help that a lot of the numbers on the internet about this are not correct based on reading a stack of the original early papers and long discussions with chatgpt about it.

Sema is most potent on GLP-1, followed by reta then tirz, but tirz ( but not reta ) has biased affinity on GLP-1 so its maximal downstream effects on target cells is going to be larger than it would seem just from the binding affinity, and the dose is 5-10 higher, so it is really hard to say which activates glp-1 the most, it is definitely possible it is tirz, not sema or reta, once adjusted for doses, and accounting for the biased affinity.

The major reason tirz and reta have less GI side effects than sema is the GIP agonism , that counteracts some of the GLP-1 adverse effects, so for most people, most of the time they are better choices as they cause more weight loss and have less side effects. This is strongest for tirz and is likely the main reason it has the lowest side effect rates, as well as the effects of the biased agonism on GLP-1 reduce adverse effects as well, though the mechanism for this I find a bit confusing.

I would expect based on this that most people would be better off on higher dose of tirz or reta than lower doses with some sema added in, but if experimentation proves otherwise, I won't argue, GLP responses do seem pretty individual at times, no doubt there is a stack of receptor polymorphism in the incretin receptors and variation in the downstream pathways as well.

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I understand your train of thought and you are correct in saying that tirzepatide is a biased agonist of GLP1R which selectively activates the cAMP pathway while avoiding b-Arrestin mediated receptor internalization. Semaglutide on the other hand is a balanced GLP1R agonist which simultaneously activates both pathways and therefore does induce receptor internalization.

One thing to take into account is that both reta and tirz are fundamentally based on the GIP peptide while sema is based on GLP1. For all intents and purposes sema IS GLP1 with two modifications which drastically increases its half life and albumin binding providing constant, time-dependent stimulation of GLP1R, just like tirz and reta. However, unlike what you said, despite the balanced agonism of sema, all functional in vitro and in vivo assays such as EC50 and ki indicate much stronger potency of sema at GLP1R and one reason why higher tirz dosages are tolerated with less side effects is specifically that tirz is lower in efficiency at GLP1R despite its biased agonism. GIPR activation is devoid of these side effects and has anti emetic effects. So its a synergy imo of reduced GLP1R activation which results in lower nausea, lower stimulation of the GI tract, vomiting and delayed gastric emptying along with antiemetic effects of GIPR activation that results in lower side effect burden.

So this is my understanding. Of course its impossible to say exactly which effect of tirz/reta is most dominant in reducing side effect burden but strong GLP1R is arguably more potent in inducing side effects than GIPR is in reducing them. At least thats my interpretation of the data available.

Either way, empirically my combo has allowed a 30% weight loss which is higher than the average weight loss seen in participants using 12mg of reta while I only use 10mg. Also observed higher HbA1c reductions (2.6% which is huge imo).

So all in all i can say the reta/sema combo worked for me though I got stuck at 30% weight loss. Now with elora 1mg i hit 35.5% weight loss which is why im ecstatic about it. Couldnt be happier and have no side effects (i did have side effects initially like nausea and sulfur burps on sema alone which lasted about a month in).

Hope this helps to all those interested in my protocol and thanks to lessthanhalf for bringing this up. Its certainly a worthwhile discussion.

Cheers!
 
Devilseye said:


I’ve been so disappointed by cagri. For one it activates calcitonin receptors that are present in the thyroid. Not ideal as calcitonin doesnt do anything for weight loss. Second, its affects are relatively short lived.

Some context first. Ive been on a combo of reta/sema (10mg/2mg because sema is covered by my insurance and reta is poor activator of GLP-1R too) and I stalled at about 30% weight loss. Ive been trying for two months to loose tge last ten pounds without success. I just kept stable at 30% flat. Cagri didnt do much difference either. Hunger curbed initially but effects didnt last it helped get me to 30% but then I took it out and no difference.

Enter eloralintide. Hunger curbed at initial 1mg dose significantly. Btw, 1mg was enough to loose my 10lbs. Even in clinical trials 1mg gave 10% bodyweight loss and 3mg barely gave better at about 12.5%. Only 9mg doubled the weight loss at 20% but ill never need that. Plus eloralintide doesnt activate calcitonin receptor. Its a winner for me.

All in all very happy with this trial. I just wish more distributors would have it accessible at their US/Canada warehouses. Id definitely buy. Right now i only see it on china warehouses.

Cheers!

Click to expand...
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Devilseye said:


I understand your train of thought and you are correct in saying that tirzepatide is a biased agonist of GLP1R which selectively activates the cAMP pathway while avoiding b-Arrestin mediated receptor internalization. Semaglutide on the other hand is a balanced GLP1R agonist which simultaneously activates both pathways and therefore does induce receptor internalization.

One thing to take into account is that both reta and tirz are fundamentally based on the GIP peptide while sema is based on GLP1. For all intents and purposes sema IS GLP1 with two modifications which drastically increases its half life and albumin binding providing constant, time-dependent stimulation of GLP1R, just like tirz and reta. However, unlike what you said, despite the balanced agonism of sema, all functional in vitro and in vivo assays such as EC50 and ki indicate much stronger potency of sema at GLP1R and one reason why higher tirz dosages are tolerated with less side effects is specifically that tirz is lower in efficiency at GLP1R despite its biased agonism. GIPR activation is devoid of these side effects and has anti emetic effects. So its a synergy imo of reduced GLP1R activation which results in lower nausea, lower stimulation of the GI tract, vomiting and delayed gastric emptying along with antiemetic effects of GIPR activation that results in lower side effect burden.

So this is my understanding. Of course its impossible to say exactly which effect of tirz/reta is most dominant in reducing side effect burden but strong GLP1R is arguably more potent in inducing side effects than GIPR is in reducing them. At least thats my interpretation of the data available.

Either way, empirically my combo has allowed a 30% weight loss which is higher than the average weight loss seen in participants using 12mg of reta while I only use 10mg. Also observed higher HbA1c reductions (2.6% which is huge imo).

So all in all i can say the reta/sema combo worked for me though I got stuck at 30% weight loss. Now with elora 1mg i hit 35.5% weight loss which is why im ecstatic about it. Couldnt be happier and have no side effects (i did have side effects initially like nausea and sulfur burps on sema alone which lasted about a month in).

Hope this helps to all those interested in my protocol and thanks to lessthanhalf for bringing this up. Its certainly a worthwhile discussion.

Cheers!

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Thank you for sharing! I just tried Eloralintide and WOW! It is a wonder drug! I lost 5 pounds in a week. I had no side effects except I was not hungry! No nausea, no GI problems, nothing. It’s amazing!
 
Tinkerbell2222 said:


Thank you for sharing! I just tried Eloralintide and WOW! It is a wonder drug! I lost 5 pounds in a week. I had no side effects except I was not hungry! No nausea, no GI problems, nothing. It’s amazing!

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My pleasure! To be clear I dont think its a replacement for GLP1s at all but it certainly helped me break through a very strong plateau!!
 
All this talk from you guys makes me excited to Elora out but I'm far from maxing out on Reta. Right now my plan would be to test adding it at ~8mg Reta but I'm titrating slowly and focusing on resistance training and protein.
 
GiffMeReta said:


All this talk from you guys makes me excited to Elora out but I'm far from maxing out on Reta. Right now my plan would be to test adding it at ~8mg Reta but I'm titrating slowly and focusing on resistance training and protein.

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Elora would max out my budget right now! Too $$$. I'll patiently wait out more options and better pricing. You kids go ahead, though, enjoy and report back. 🤣
 
spanky2026 said:


Never would have thought of adding low dose sema to tirz. Interesting

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Yes I have never tried Sema (tried reta for two months sleep was terrible). Now I am doing Tirz but would consider adding semi...
 
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