Matching average levels of Reta and Tirz?

[TropicalBlaster]

I'm titrating Tirz down (currently at 15 mg) and Reta up (currently at 2 mg).

Should I be trying to hold the same average amount og GLP-1 peptide each day?

At 15mg Tirz I'm sat around 24mg on injection day, falling to roughly 10mg before the next jab. That works out to a 7 day running average of 16.5mg of Tirz.

I've since gone down to 12.5mg Tirz, and I'm on 2mg Reta. Planning to raise it to 3mg Reta, which would give a 17.5mg 7-day running average. Is that the right way to go about it? should I be looking at the running average of the combination of the two GLP-1s?

 

[woundcarping]

TropicalBlaster said:


I'm in the process of reducing Tirz and upping Reta, but I was worried about having too much.

I was on Tirz 15, but I've just dropped to 12.5 and taking 2mg Reta this week.

Plan to get to 12.5mg Tirz and 4mg Reta in a few weeks and see how it goes...

I've made a graph to try and track the does, I didn't want to go above the '27mg' of GLP-1s in my system when I was injecting the 15mg Tirz and wanted the average in body to maintain around 18/19mg. However, it seems like your all going way beyond that! Have there been any published studies around what levels are safe?

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This isn't a case of stacking 2 GLP1s — what you've got is a GLP1/GIP paired with a GLP1/GIP/GCG. Their receptor signaling ratios don't match.

Those graph levels look precise, but from what I can tell they're largely, maybe even wholly, relative, and close to useless when it comes to judging a dose. What led you to decide 27mg was the ceiling you didn't want to cross?

If peak is the only thing capping you, then splitting the dose would allow 20-30% higher dosing, which would raise your average exposure by roughly the same amount.

My own path was bridging from Tirz to Reta, and I raised my dose mostly according to sides and efficacy.

 

[eidos]

That's not how it works. Tirz and Reta don't engage the GLP-1 receptor in the same manner, which is exactly what @woundcarping pointed out.

Half-lives and time to peak concentration are figures derived from averages, and across the populations studied the standard deviations run around 1 day.

Receptor genetics differ between individuals, so affinities aren't uniform from one person to the next.

No equivalence can be worked out, because Tirz acts as a "biased agonist" at the GLP-1 receptor.

Bottom line: stop overanalyzing. While you're raising the dose, track how things actually go for you: weight loss, given that this seems to be your primary objective; blood sugar, since hypoglycemia is a possibility and you're better off knowing about it; side effects; the routine checks, blood pressure and heart rate, plus bloodwork every few months.

 

[Gwynhwyfar]

Took the identical route: began at 15 MG Tirz, currently down to 7.5 MG, adding 2x3 MG Reta on top. Feels dialled in at the moment, and my first set of labs after just under 2 months on Reta lands Tuesday.

 

[Devilseye]

Here's a look at how these compounds bind to GLP1, GIP, and GCGR receptors.

Tirzepatide's GLP1 activity is roughly 2 times that of retatrutide and semaglutide, and those 2 are basically on par with each other.

Native GLP1, meanwhile, hits the GLP1 receptor with about 10 times the potency of tirzepatide.

So they differ from one another.

 

[TropicalBlaster]

Appreciate everyone's replies! Now I'm off to dig up additional details to plug into my spreadsheets. Maybe I'll even chart how strongly each receptor type binds at the Tirz and Reta levels.

woundcarping said:


Why the 27mg?

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All I really knew was that I felt no side effects at all with that much peptide in my system, and since that was the top Tirz dose the studies recommended, I figured keeping under it would be safe. (Though I realize they're testing bigger doses these days.)

After reading the other posts about this, I think I'm ready to go up on my doses now.

Devilseye said:

Here's a look at how these compounds bind to GLP1, GIP, and GCGR receptors.

Tirzepatide's GLP1 activity is roughly 2 times that of retatrutide and semaglutide, and those 2 are basically on par with each other.

Native GLP1, meanwhile, hits the GLP1 receptor with about 10 times the potency of tirzepatide.

So they differ from one another.

Thanks for passing this along! This was the piece I lacked... I knew the receptors differed, but not how potent each compound is at each one. Now I'm going to look into precisely why they differ and deepen my grasp

 

[woundcarping]

TropicalBlaster said:


Potentially tracking the affinity for each receptor type for the levels of Tirz and Reta…

…Now I'm going to research exactly why they are different and improve my understanding

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Trying to forecast doses from EC50 or Emax just doesn't work in practice. The science is too loose for that, and there's no way to know how those numbers translate to your own body.

Digging deeper than average is fine by me, but applying this data the way you are looks like serious overthinking. Whether your endgame is running both together or making Reta your main peptide, I can't tell. Broadly speaking, you dose up to the point where it works, and side effects set the ceiling.

When you're making a switch, the pace can be as fast as your own tolerance for sides permits... taking many small doses through the changeover tends to make side effects show up less sharply than if you take bigger doses spaced far apart and then have to ride them out.

My own move was 5mg Tirz up to 18mg Reta across 17 weeks with barely any bad sides, and the effect stayed steady and where I wanted it through the 27 weeks I've been on Reta.