Switching from Tirz + Reta to another stack

[cloratheshadow]

Thinking about swapping my Tirz for Sema. Reta has treated me well so far, and right now I’m on 8.5 mg Tirz plus 4mg Reta. I’d like to make Reta the main focus and bring Tirz down. That got me wondering…

Tirz has less GLP-1 than Sema and Reta

Tirz also has less GIP than Reta

So wouldn’t it save more money to simply replace Tirz with Reta? Reta already covers everything I need, and throwing in a little Sema for extra satiety seems like the simpler route. Sema costs almost nothing, kits run about $50.

Any reason I shouldn’t?

 

[cheaperseeker]

The sides on sema hit hard. I ended up keeping ginger beer in the fridge for the nausea, and that was still true 9 months in

 

[cloratheshadow]

cheaperseeker said:

The sides on sema hit hard. I ended up keeping ginger beer in the fridge for the nausea, and that was still true 9 months in

Nausea has pretty much been a constant for me and it doesn’t really bother me (I deal with vertigo)

How about microdosing?

 

[cheaperseeker]

cloratheshadow said:

cheaperseeker said:

The sides on sema hit hard. I ended up keeping ginger beer in the fridge for the nausea, and that was still true 9 months in

Nausea has pretty much been a constant for me and it doesn’t really bother me (I deal with vertigo)

How about microdosing?

Sulfur burps were awful too, along with diarrhea, stomach cramps, and fatigue.

There's no harm in giving it a shot to find out how your body responds.

 

[bada bing]

It's said that Tirz's GIP agonism is what blunts its unwanted GLP1 side effects, which would explain why it's tolerated better than Sema. Reta shares that same GIP agonism. In theory, combining Sema with Reta might be tolerated better than Sema on its own, while delivering a more precisely targeted GLP1 boost.

A slow, cautious trial is definitely worth it. I picked up a 5mg Sema kit specifically for that purpose, in case I ever need it. Sema is inexpensive and keeps very well in the freezer. A time may come when it's obsolete and hard to source, so I treat it as a cheap contingency investment.

 

[AllCourtTENNIS]

Began with tirz, hit a plateau around 2 months while on 12.5mg each week, and then added reta on top. Now I'm at a lower tirz dose plus 10mg reta. Progress is happening, just not quickly. Plenty of others have seen much bigger numbers with this combo, but honestly I feel amazing versus 1 year ago.

Sema has been something I steered clear of, since every person I know irl who gave it a go dealt with awful GI side effects.

Edit: lol my signature displays my stack and I blanked on that

 

[Flash-BCR]

bada bing said:

It's said that Tirz's GIP agonism is what blunts its unwanted GLP1 side effects, which would explain why it's tolerated better than Sema. Reta shares that same GIP agonism. In theory, combining Sema with Reta might be tolerated better than Sema on its own, while delivering a more precisely targeted GLP1 boost.

A slow, cautious trial is definitely worth it. I picked up a 5mg Sema kit specifically for that purpose, in case I ever need it. Sema is inexpensive and keeps very well in the freezer. A time may come when it's obsolete and hard to source, so I treat it as a cheap contingency investment.

I also have sema on hand, and for that same reason...I doubt I'll ever end up using it. The cost was $45 per kit for 5mg...

 

[Panderas785]

cheaperseeker said:

cloratheshadow said:

cheaperseeker said:

The sides on sema hit hard. I ended up keeping ginger beer in the fridge for the nausea, and that was still true 9 months in

Nausea has pretty much been a constant for me and it doesn’t really bother me (I deal with vertigo)

How about microdosing?

Sulfur burps were awful too, along with diarrhea, stomach cramps, and fatigue.

There's no harm in giving it a shot to find out how your body responds.

I was on sema for close to 6 months, and even then I’d still occasionally get hit with unexpected burps and diarrhea. There was a stretch of roughly 6 weeks with no issues, then out of nowhere it came back. These days I’m only doing split doses of Reta, and it seems like I don’t get any side effects at all.

 

[HARLEYV2]

Starting 3 mg Reta this evening, then 1 mg tirz comes in on Sunday. Next Wednesday it's 4 mg Reta, with 1 mg Tirz again on Sunday. Has anyone had any joy with a stack like this ?

 

[lessthanhalf]

cloratheshadow said:

Thinking about swapping my Tirz for Sema. Reta has treated me well so far, and right now I’m on 8.5 mg Tirz plus 4mg Reta. I’d like to make Reta the main focus and bring Tirz down. That got me wondering…

Tirz has less GLP-1 than Sema and Reta

Tirz also has less GIP than Reta

So wouldn’t it save more money to simply replace Tirz with Reta? Reta already covers everything I need, and throwing in a little Sema for extra satiety seems like the simpler route. Sema costs almost nothing, kits run about $50.

Any reason I shouldn’t?

There is indeed a rationale against doing that. What you find online regarding receptor affinities across the various GLP drugs tends to be muddled and inconsistent. The biggest factor is who performed the measurement, the method used, and whether albumin was bound during testing (within the body, 99% of it is albumin-bound). Much of this data sits in preclinical papers under development code names, not the commercial names.

Having gone through a stack of papers on the subject, tirzepatide shows the strongest GIP agonism, not reta, and I think that is the primary explanation for why tirz has the fewest side effects among all the GLP drugs, once you adjust for how well it drives weight loss. The GIP agonism offsets many of the GLP-1 adverse effects such as nausea, vomiting, GI issues, malaise and food aversion. If reta genuinely had stronger GIP agonism than tirz, it ought to produce fewer GI side effects, and it does not.

When it comes to GLP-1 receptors, semaglutide is more potent than tirz or reta, but other factors are at play. tirz and reta are dosed higher, which narrows that gap, and tirz acts as a biased agonist at GLP-1, which lets it generate larger downstream effects from GLP-1 agonism even with lower affinity.

So in that equation, replacing tirz with sema should cut GIP agonism considerably, which would worsen the side effects coming from reta, and I doubt reta's weaker GIP agonism would do much to ease the GLP-1 side effects of sema, since reta on its own has stronger GLP-1 side effects than tirz.

So the net result would be somewhat more GLP-1 agonism, depending on dose, though even that is not 100% certain given the biased agonism point, plus far less GIP, and unchanged glucagon. That means more gastrointestinal side effects and weaker weight loss, since tirz outperforms sema at producing weight loss.

What you are already taking will outperform sema/reta, depending on your goal in rearranging them, whether that is more weight loss or fewer side effects. Raising the dose of either reta or tirz would probably curb hunger and boost weight loss, which makes the most sense and is the simplest path. If you still have substantial weight to lose, adding low dose cagri or elora is another route, but I would raise reta or tirz first, unless side effects at current doses are the issue.

 

[woundcarping]

lessthanhalf said:

cloratheshadow said:

Thinking about swapping my Tirz for Sema. Reta has treated me well so far, and right now I’m on 8.5 mg Tirz plus 4mg Reta. I’d like to make Reta the main focus and bring Tirz down. That got me wondering…

Tirz has less GLP-1 than Sema and Reta

Tirz also has less GIP than Reta

So wouldn’t it save more money to simply replace Tirz with Reta? Reta already covers everything I need, and throwing in a little Sema for extra satiety seems like the simpler route. Sema costs almost nothing, kits run about $50.

Any reason I shouldn’t?

There is indeed a rationale against doing that. What you find online regarding receptor affinities across the various GLP drugs tends to be muddled and inconsistent. The biggest factor is who performed the measurement, the method used, and whether albumin was bound during testing (within the body, 99% of it is albumin-bound). Much of this data sits in preclinical papers under development code names, not the commercial names.

Having gone through a stack of papers on the subject, tirzepatide shows the strongest GIP agonism, not reta, and I think that is the primary explanation for why tirz has the fewest side effects among all the GLP drugs, once you adjust for how well it drives weight loss. The GIP agonism offsets many of the GLP-1 adverse effects such as nausea, vomiting, GI issues, malaise and food aversion. If reta genuinely had stronger GIP agonism than tirz, it ought to produce fewer GI side effects, and it does not.

When it comes to GLP-1 receptors, semaglutide is more potent than tirz or reta, but other factors are at play. tirz and reta are dosed higher, which narrows that gap, and tirz acts as a biased agonist at GLP-1, which lets it generate larger downstream effects from GLP-1 agonism even with lower affinity.

So in that equation, replacing tirz with sema should cut GIP agonism considerably, which would worsen the side effects coming from reta, and I doubt reta's weaker GIP agonism would do much to ease the GLP-1 side effects of sema, since reta on its own has stronger GLP-1 side effects than tirz.

So the net result would be somewhat more GLP-1 agonism, depending on dose, though even that is not 100% certain given the biased agonism point, plus far less GIP, and unchanged glucagon. That means more gastrointestinal side effects and weaker weight loss, since tirz outperforms sema at producing weight loss.

What you are already taking will outperform sema/reta, depending on your goal in rearranging them, whether that is more weight loss or fewer side effects. Raising the dose of either reta or tirz would probably curb hunger and boost weight loss, which makes the most sense and is the simplest path. If you still have substantial weight to lose, adding low dose cagri or elora is another route, but I would raise reta or tirz first, unless side effects at current doses are the issue.

Tomorrow marks 8 weeks since I began stacking Sema alongside a healthy Reta dose. Over that stretch I've used 1.8mg of Sema in total (averaging .225mg per week) plus 118mg of Reta.

I've dropped exactly 20lb, though part of that comes from water loss after I quit creatine. Since adding Sema, the sides have without question been the worst I've dealt with… that said, they aren't objectively severe, just more than anything I experienced when I was on Tirz and later moved to Reta.

Escalating the dose is no small matter. My very first pin was .25mg, which killed my appetite and left me feeling bleh, so I pushed back my following Reta dose until I felt level again. Since that first pin I've been splitting the dose into .125mg 2x per week. On Sunday I raised it to .1875mg, and Monday became the first time in years I threw up. I was taking pills at the time and it may have just tickled my throat, so I can't put all the blame on Sema… the bleh feeling did come back stronger though, so Sema is likely the culprit.

Anyway, what I have on hand is more than a decade's worth of my Sema dose. I'm considering a switch from Sema over to Tirz, since I know it's the smoother one.