Changing my stack from Tirz + Reta to…

cloratheshadow

cloratheshadow

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Considering switching my Tirz out for Sema. So far Reta has been really good and I’m currently at 8.5 mg Tirz and 4mg Reta. I’m kind of wanting to focus on Reta and lowering Tirz. But it had me thinking…

If Sema has more GLP-1 than Tirz and Reta

And Reta has more GIP than Tirz

Wouldn’t it be more cost effective to just switch my Tirz for Reta? I’m already getting everything with Reta, so adding a small bit of Sema to it for added satiety sounds easier to me. Sema is so cheap, kits are like $50.

Is there any reason not to?
 
cheaperseeker said:


Sema side effects are strong. I had to keep ginger beer in the house to deal with the nausea, even after I had been on it for 9 months

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I’ve kind of always dealt with nausea and I don’t really mind it (I struggle with vertigo)

What about microdosing?
 
cloratheshadow said:


I’ve kind of always dealt with nausea and I don’t really mind it (I struggle with vertigo)

What about microdosing?

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Diarrhea, stomach cramps, fatigue, and sulfur burps were also a problem. Ugh sulfur burps were terrible.

You could always try it out and see how it affects you.
 
Supposedly the GIP agonism in Tirz has the effect of moderating it's unwanted GLP1 side effects, which is an explanation of why it is better tolerated than Sema. The same GIP agonism is true for Reta. Hypothetically mixing Sema with Reta could have better tolerability than Sema alone while giving a more narrowly targeted boost in GLP1 effects..

It certainly is worth a slow careful try. I have a 5mg Sema kit I bought for just that use, if the need ever arises. Sema is cheap and stores very well in the freezer. There may come a time when it's obsolete and hard to source, so I consider it a cheap contingency investment.
 
I started on tirz, plateaued for about 2 months at 12.5mg weekly, then started stacking with reta. I'm down to lowish dose tirz and 10mg reta. I'm losing but slowly. Others have had far more numerical success on this stack, but omg I feel so good compared to a year ago.

I've avoided sema because everyone I know irl who tried it had horrible GI side effects.

Edit: lol I forgot my signature shows my stack
 
bada bing said:


Supposedly the GIP agonism in Tirz has the effect of moderating it's unwanted GLP1 side effects, which is an explanation of why it is better tolerated than Sema. The same GIP agonism is true for Reta. Hypothetically mixing Sema with Reta could have better tolerability than Sema alone while giving a more narrowly targeted boost in GLP1 effects..

It certainly is worth a slow careful try. I have a 5mg Sema kit I bought for just that use, if the need ever arises. Sema is cheap and stores very well in the freezer. There may come a time when it's obsolete and hard to source, so I consider it a cheap contingency investment.

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I have sema also for the same reason...and am not sure if I will ever use it. It was $45 a kit for 5mg...
 
cheaperseeker said:


Diarrhea, stomach cramps, fatigue, and sulfur burps were also a problem. Ugh sulfur burps were terrible.

You could always try it out and see how it affects you.

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Even after sema for almost six months. Would still get the random burps and runs at times. Went about six weeks no sides then bam, surprise ! Now I’m just split dosing Reta. I feel like I get no sides.
 
I'm doing 3 mg Reta tonight, adding 1 mg tirz Sunday. Plan on 4 mg Reta next Wednesday and 1 mg Tirz on Sunday. Anyone had any luck with this kind of stack ?
 
cloratheshadow said:


Considering switching my Tirz out for Sema. So far Reta has been really good and I’m currently at 8.5 mg Tirz and 4mg Reta. I’m kind of wanting to focus on Reta and lowering Tirz. But it had me thinking…

If Sema has more GLP-1 than Tirz and Reta

And Reta has more GIP than Tirz

Wouldn’t it be more cost effective to just switch my Tirz for Reta? I’m already getting everything with Reta, so adding a small bit of Sema to it for added satiety sounds easier to me. Sema is so cheap, kits are like $50.

Is there any reason not to?

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Yes there is a reason not to. The info online about receptor affinities for the different GLP drugs is confusing and contradictory. Mainly as it depend a lot on who measured it and how and was it bound to albumin when it was tested ( in the body 99% of it is bound to albumin. ) Most of this info is in the preclinical papers under the drug development code names rather than under their sales names.

After reading a pile of papers on this, Tirzepatide has the strongest GIP agonism, not reta and I believe this is the main reason why tirz has the least side effects of all the GLP drugs, adjusted for weight loss effectiveness. The GIP agonism counteracts a lot of the GLP-1 adverse effects of nausea , vomiting , GI effects, malaise and food aversion. If reta really had stronger GIP agonism than tirz , it should cause less GI side effects and it does not.

Semaglutide is more potent at GLP-1 receptors than tirz or reta, but there are other factors. tirz and reta are used at higher doses , reducing this difference, and tirz is a biased agonist at GLP-1, allowing it to have larger downstream effects from the GLP-1 agonism, despite the lower affinity.

So I would expect swapping tirz for sema in that equation to substantially reduce GIP agonism, which would increase the side effects from reta, and I do not think the lower GIP agonism of reta would help a lot with the GLP -1 side effects from sema, as reta itself has stronger GLP-1 side effects than tirz.

So the main effect would be a bit more GLP-1 agonism , depending on the dose, though even this is not 100% clear given the biased agonism bit, and a lot less GIP , and the same glucagon. So more gastrointestinal side effects, and less weight loss effectiveness, given that tirz is better at causing weight loss than sema.

Depending on what you want to achieve by changing them around, more weight loss or less side effects?, what you are on will work better than sema/reta. Increasing the dose of either reta or tirz would likely reduce hunger and increase weight loss and makes the most sense and is simplest. Adding in low dose cagri or elora is another option if you still have a lot of weight left to lose, but I would increase reta or tirz first, unless side effects are the problem at current doses.
 
lessthanhalf said:


Yes there is a reason not to. The info online about receptor affinities for the different GLP drugs is confusing and contradictory. Mainly as it depend a lot on who measured it and how and was it bound to albumin when it was tested ( in the body 99% of it is bound to albumin. ) Most of this info is in the preclinical papers under the drug development code names rather than under their sales names.

After reading a pile of papers on this, Tirzepatide has the strongest GIP agonism, not reta and I believe this is the main reason why tirz has the least side effects of all the GLP drugs, adjusted for weight loss effectiveness. The GIP agonism counteracts a lot of the GLP-1 adverse effects of nausea , vomiting , GI effects, malaise and food aversion. If reta really had stronger GIP agonism than tirz , it should cause less GI side effects and it does not.

Semaglutide is more potent at GLP-1 receptors than tirz or reta, but there are other factors. tirz and reta are used at higher doses , reducing this difference, and tirz is a biased agonist at GLP-1, allowing it to have larger downstream effects from the GLP-1 agonism, despite the lower affinity.

So I would expect swapping tirz for sema in that equation to substantially reduce GIP agonism, which would increase the side effects from reta, and I do not think the lower GIP agonism of reta would help a lot with the GLP -1 side effects from sema, as reta itself has stronger GLP-1 side effects than tirz.

So the main effect would be a bit more GLP-1 agonism , depending on the dose, though even this is not 100% clear given the biased agonism bit, and a lot less GIP , and the same glucagon. So more gastrointestinal side effects, and less weight loss effectiveness, given that tirz is better at causing weight loss than sema.

Depending on what you want to achieve by changing them around, more weight loss or less side effects?, what you are on will work better than sema/reta. Increasing the dose of either reta or tirz would likely reduce hunger and increase weight loss and makes the most sense and is simplest. Adding in low dose cagri or elora is another option if you still have a lot of weight left to lose, but I would increase reta or tirz first, unless side effects are the problem at current doses.

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I started stacking Sema with a healthy dose of Reta 8 weeks ago as of tomorrow. I’ve taken a total of 1.8mg of Sema (.225mg/week average) and 118mg of Reta in that time.

I’m down an even 20lb, some of that is dewatering after stopping creatine. I’ve absolutely had the worse sides since stacking Sema… overall they have not been objectively bad, just the most I’ve had since starting on Tirz then switching to Reta.

Dose escalation is a serious thing. My first pin was .25mg which flattened my appetite and made me feel like bleh, I delayed my next Reta dose until I’d evened out. I’ve been split dosing .125mg 2x weekly since the first pin. Sunday I bumped my dose to .1875mg and Monday was the first time I’ve thrown up in years. I was swallowing pills and maybe it tickled my throat or something, can’t entirely blame Sema… I did have more of that bleh feeling, so Sema is probably to blame.

Anyways, I have a more than decade of my Sema dose on hand. I am thinking about switching from Sema to Tirz, I know it’s a smoother experience.
 
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