Stacking Tirz & Reta: what's your long-term plan?

Starting in June, I moved from 100% Tirz to 100% Reta across 8 weeks, going from 5mg/week Tirz to 4mg/week Reta. Just my opinion, but for me they cover the same ground, with a few differences in how they feel. Having tried each on its own, I lean slightly toward Tirz. I can see how Reta might have an edge during the weight loss phase.

I have roughly 5ish years of each stocked up, so I'll likely alternate or stack them. For the next year I'm probably staying on straight Reta, and after that I haven't decided.

trey915 said:

My current stack is 5mg Tirz, 5mg Reta, and 1.5mg Cagri. There's still some noise, but it's manageable, and I'm able to get my calories and nutrients in. I'm no longer in a deficit—right now I'm just focused on building muscle mass—but so far this combination is working well for me. I've been stacking Tirz with Reta for roughly 8 weeks (4 of those with Cagri). I began at 15mg Tirz and lowered it each week while raising Reta each week. I knew I wanted at least 4mg Reta to get solid glucagon effects.

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Forgive my ignorance — I'm new to this and curious about trying Reta, so I'd like to understand the reasoning: since Reta and Tirz do similar jobs, why would someone use both at the same time?

bada bing said:

Starting in June, I moved from 100% Tirz to 100% Reta across 8 weeks, going from 5mg/week Tirz to 4mg/week Reta. Just my opinion, but for me they cover the same ground, with a few differences in how they feel. Having tried each on its own, I lean slightly toward Tirz. I can see how Reta might have an edge during the weight loss phase.

I have roughly 5ish years of each stocked up, so I'll likely alternate or stack them. For the next year I'm probably staying on straight Reta, and after that I haven't decided.

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I'm in the same boat for maintenance: tirz is my primary, and I bring reta in on a rotating basis whenever it's needed. That said, reta worked better for actual weight loss — it simply needed some time to build up.

i4short said:

Forgive my ignorance — I'm new to this and curious about trying Reta, so I'd like to understand the reasoning: since Reta and Tirz do similar jobs, why would someone use both at the same time?

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Based on what I've picked up from this community, Reddit and other places, the appeal seems to be combining reta's extra glucagon effect with tirz's stronger suppression of appetite and food noise, which people say feels weaker on reta.

Honestly, I probably need to dig into the research more. Looking at it strictly from a biochemical angle, I can't quite see what taking two compounds aimed at the same receptors actually gets you. Perhaps each one only partially activates the receptor, so together they work in a complementary way instead of fighting each other.

LetsGoWolves said:

Honestly, I probably need to dig into the research more. Looking at it strictly from a biochemical angle, I can't quite see what taking two compounds aimed at the same receptors actually gets you. Perhaps each one only partially activates the receptor, so together they work in a complementary way instead of fighting each other.

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From what people report, Sema appears to work best for suppressing appetite.

All 3 GLP1 peptides include a GLP1 agonist, and Sema's stronger agonist action seems to be at the GLP1 receptor.

A number of people combine sema with Tirz or Reta.

If you look at a Tirz/Reta stack, you're again layering GLP1 and GIP, then adding Reta's Glucagon component.

These aren't different versions of one peptide; each stands on its own, but each brings a different agonist.

So on the chart, where a smaller number means stronger, you can see why stacking might offer some advantage.

That said, stacking isn't necessary for everyone. I reached goal on Tirz by itself, though I responded quite well.

Others find they need an amylin agonist such as Cagri or Elora added in.

I began with Tirz and later added Reta — honestly, mostly out of FOMO. Now I'm switching back to 100% Tirz. The side effects are more intense for me on Reta, and the bad sleep was really taking a toll. On top of that, there's a solid chance I can reach my goal weight using Tirz by itself, so there's no reason to make things more complicated.

LetsGoWolves said:

Honestly, I probably need to dig into the research more. Looking at it strictly from a biochemical angle, I can't quite see what taking two compounds aimed at the same receptors actually gets you. Perhaps each one only partially activates the receptor, so together they work in a complementary way instead of fighting each other.

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Because reta and tirz differ in how strongly they act on GLP-1 versus GIP, and glucagon receptors are only touched by reta, pairing them at below-max doses can in effect create a hybrid medication that ideally delivers benefits from both while perhaps reducing side effects. Take someone who gets an excessive rise in heart rate or anhedonia from reta above 6mg yet remains overweight or hungry: adding tirz could help them, and may work better than simply switching. That said, your main point holds—most of what the two do overlaps.

Personally, I was at 15mg of tirz and still hungry (I only began GLP drugs after losing 70kg), so I added roughly 6mg of reta, which helped. I'm now on 15 of tirz plus 8mg of reta, but going higher brings on very unpleasant skin pain, and reta seems to trigger that more than tirz does for me; this dose is close to weight neutral, so it isn't excessive even though the combination exceeds the standard maximum.

With elora now available and the early tirz plus elora study results looking amazing, adding elora to tirz or reta seems to make more sense than combining the two.

I get that these are distinct compounds, but they're related and they act biochemically on the same receptors. Elsewhere in medicine, we wouldn't pair two drugs hitting the same receptors, since the likely outcome is competition for binding sites rather than a boost in effect.

Take hypertension: you typically wouldn't prescribe two different ACE inhibitors or two different calcium channel blockers. If one agent fails to bring blood pressure into goal range, you'd add one from a different class.

Looking at your chart, there's a theoretical case for pairing sema with tirz, given that tirz is only a partial agonist at GLP-1r. But in theory at least, adding tirz or sema to reta shouldn't offer any advantage, because reta is a full agonist at all 3 receptors it targets. Whatever receptors tirz or sema occupy would simply be unavailable for reta to engage.

That's why I mentioned I need to dig deeper into the research. The straightforward biochemistry of stacking them doesn't add up to me.

i4short said:

Forgive my ignorance — I'm new to this and curious about trying Reta, so I'd like to understand the reasoning: since Reta and Tirz do similar jobs, why would someone use both at the same time?

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I've been on both since March - April. Over that stretch I've tried higher doses of just one or the other, and also taken them together. For me, the combo of both gives the best results.

Since I don't hit the magic 4mg or higher reta dose, I'm not sure whether I'm getting glucagon effects, or whether the two are synergistic. What I do know is that taking both makes something feel different and better. When deciding what to take and how much, I've always leaned more on the practical than the theoretical.

I'm running both Reta and Tirz together, though I'm shifting the balance toward tirz because the higher resting heart rate from Reta never leveled off. I began at reta 6mg plus tirz 3mg, and I expect to land near Reta 4mg with Tirz 5-5.5mg. A full switch to Tirz alone is tempting, but Reta has cut my triglycerides remarkably well, and I want to hold on to that glucagon effect, even if the dose ends up smaller.