New stack

[Ashley2077]

Adding Reta to my arsenal to see if anything changes. Currently on 15mg tirz weekly but going to taper down. Started cagri .25mg last week and started 1mg Reta today. Anyone else doing something similar? Goal is to be on less tirz and perhaps start a more efficient routine.

 

[Pinmebaby1moretime]

I stopped Tirz before pinning Reta best practice is to wait a bit until it’s out of your system before switching

 

[Calm Logic]

I plan to slowly transition:

That seems to be the common starting out Reta experience - more hunger and people eating more, but they report still losing once you get up to the higher doses (6mg+) - lot of people saying youll gain a little back during the transition but itll work itself out on the other side after a couple months on reta. It looks like the reta suppression doesnt really kick in until those higher doses, so thats why so many end up stacking some tirz.

 

[Ashley2077]

I stopped Tirz before pinning Reta best practice is to wait a bit until it’s out of your system before switching

Any specific reasoning to wait until the tirz is out of your system? Is it because both are competing for many of the same receptors and possibly cancel some of each out?

 

[Calm Logic]

The approach by @Pinmebaby1moretime of switching rather than transitioning/stacking would be more medically sound / conservative / safe (even though reta is not FDA appoved yet). And the more I think about it, it seems more attractive to me since the path would be clearer. And Google Gemini agrees:

The more commonly accepted and safer strategy (assuming retatrutide approval and guidelines) would be:

1. Administer your last full dose of tirzepatide as scheduled.
   
   
2. On the day you would normally take your next tirzepatide dose (i.e., 7 days after the last tirzepatide injection), administer the lowest starting dose of retatrutide.
   
   
3. Follow the manufacturer's recommended titration schedule for retatrutide (likely monthly increases).
   

Why this is generally preferred:

• Overlap, Not Gap: Due to the long half-life of tirzepatide, there will naturally be a significant overlap in the presence of both drugs in your system for several weeks. This means you won't suddenly lose all GLP-1 effect when you stop tirzepatide; its levels will decline gradually.
  
  
• Minimizing Side Effects of New Drug: Starting retatrutide at its lowest dose is the primary method to manage the initial GI side effects that are common with these medications.
  
  
• Simplicity and Safety: This approach is simpler and less prone to errors or creating unintended therapeutic gaps.

Here's a chart posed by Lullabytreehugger that may help (but I have to constantly remember that lower numbers are stronger, on a log scale):



Before I saw this chart, I didn't know that reta is stronger for GIP than tirz. So reta is the clear winner in both the GIP and GCGR department (even compared to tirz with survo).

So if switching cold turkey (going completely off tirz), I don't think a washout period is needed since one normally starts on a low dose anyway, and the only concern would be reta's stronger (but dose-dependent) effect on GIP. Of course, even stopping tirz completely, you still will have tirz in your system for several weeks, gradually declining.

For transitioning by lowering the tirz while starting reta (which is what I was originally planning buy maybe not anymore), I don't know what dose schedule to use. Since it would be relatively experimental/risky, I would go slowly, at least since I could have a lot of tirz left over anyway.


More info:

Post in thread 'Considering Survodutide'

Nov 25, 2024

Had to use chatgpt...

Google isn't helping me here and I'm feeling incredibly dumb for not quite understanding what these numbers mean.

The GLP-1 K value is a measure of the binding affinity of a ligand (such as a GLP-1 receptor agonist) to the GLP-1 receptor. GLP-1 (glucagon-like peptide-1) is a hormone that plays a role in glucose metabolism, and its receptor is a target for drugs used in the treatment of type 2 diabetes and obesity.

Key points about the GLP-1 K value:​

1. Definition of K value:
   
   • The "K" generally refers to a dissociation constant...

• brentm

• 

 

[Skidude]

The approach by @Pinmebaby1moretime of switching rather than transitioning/stacking would be more medically sound / conservative / safe (even though reta is not FDA appoved yet). And the more I think about it, it seems more attractive to me since the path would be clearer. And Google Gemini agrees:


Here's a chart posed by Lullabytreehugger that may help (but I have to constantly remember that lower numbers are stronger, on a log scale):

View attachment 7168

Before I saw this chart, I didn't know that reta is stronger for GIP than tirz. So reta is the clear winner in both the GIP and GCGR department (even compared to tirz with survo).

So if switching cold turkey (going completely off tirz), I don't think a washout period is needed since one normally starts on a low dose anyway, and the only concern would be reta's stronger (but dose-dependent) effect on GIP. Of course, even stopping tirz completely, you still will have tirz in your system for several weeks, gradually declining.

For transitioning by lowering the tirz while starting reta (which is what I was originally planning buy maybe not anymore), I don't know what dose schedule to use. Since it would be relatively experimental/risky, I would go slowly, at least since I could have a lot of tirz left over anyway.


More info:

Post in thread 'Considering Survodutide'

Nov 25, 2024

Had to use chatgpt...

Google isn't helping me here and I'm feeling incredibly dumb for not quite understanding what these numbers mean.

The GLP-1 K value is a measure of the binding affinity of a ligand (such as a GLP-1 receptor agonist) to the GLP-1 receptor. GLP-1 (glucagon-like peptide-1) is a hormone that plays a role in glucose metabolism, and its receptor is a target for drugs used in the treatment of type 2 diabetes and obesity.

Key points about the GLP-1 K value:​

1. Definition of K value:
   
   • The "K" generally refers to a dissociation constant...

• brentm

• 

I was searching for that chart a few weeks ago, I love how it describes the different aspects of each.

 

[Calm Logic]

And it's easily digested by AI 🙂

From Google Gemini:

To determine an equivalent dose of Retatrutide (Reta) for 15 mg of Tirzepatide (Tirz) specifically for the GIP receptor, we can use the GIP KI values from the table you provided:

• Tirzepatide GIP KI: 0.135
• Retatrutide GIP KI: 0.057

Since "Lower # = stronger," Retatrutide is stronger at the GIP receptor than Tirzepatide.

To find how much stronger Retatrutide is for GIP:Strength Ratio = Retatrutide GIP KITirzepatide GIP KI=0.0570.135≈2.368

This means Retatrutide is approximately 2.368 times stronger than Tirzepatide at the GIP receptor.

Therefore, for an equivalent GIP effect, you would need a lower dose of Retatrutide:Equivalent Retatrutide Dose = Strength Ratio15 mg (Tirzepatide)=2.36815 mg≈6.33 mg

So, approximately 6.33 mg of Retatrutide would provide an equivalent GIP receptor activation compared to 15 mg of Tirzepatide, based solely on these in vitro KI values.

But I don't know if that calculation is accurate if the KI values are on a log scale. And whatever other assumptions are being made by using KI values in the first place.

A recalculation to consider the log scale:

Recalculating Equivalent Dose of Reta for GIP compared to 15 mg of Tirzepatide (Log Scale)​

1. GIP Receptor KI Values (from your table):

• Tirzepatide GIP KI (log scale): 0.135
• Retatrutide GIP KI (log scale): 0.057

2. Determine the Difference in Log Potency:A smaller number on this log scale means stronger potency.Difference in log scale = (Tirzepatide GIP KI) - (Retatrutide GIP KI)Difference = 0.135−0.057=0.078

3. Convert to Linear Potency Ratio:The difference on a log scale corresponds to a multiplicative factor on a linear scale. Assuming base 10 for the log scale:Linear Potency Ratio (Retatrutide vs. Tirzepatide for GIP) = 10DifferenceRatio = 100.078≈1.196

This means Retatrutide is approximately 1.196 times stronger than Tirzepatide at the GIP receptor, when considering the values on a base-10 log scale.

4. Calculate Equivalent Retatrutide Dose: Since Retatrutide is stronger, you would need a lower dose of Retatrutide for the same GIP effect. Equivalent Retatrutide Dose = 1.19615 mg (Tirzepatide)≈12.54 mg

 

[Pinmebaby1moretime]

yeah basically the GLP1 and GIP mechanism overlap between the two can cause problems- you hear ppl say receptor overload essentially you want to avoid increasing risks of side effects like hypoglycemia, GI side effects, severe nausea and dehydration etc. don’t want you to end up in the hospital for any of these.

Everyone’s tolerance of risk is different but I don’t see the point in risking here. It’s better to gain a little weight while switching and doing it slow because you will lose it and more once you are able to titrate up slowly! I’m on week two of 0.5mg Reta. I gained 3 lbs despite working out twice a day. I burn 700-900 calories and I’m eating max 1600 calories on a good day (focused on hitting my protein goal of 100g at least).

Butttt I’m not stressed. Once I get to 4mg, I know I’ll shed all this off and so much more with my healthy eating habits and exercise schedule. Also this could be water weight! Weight loss maps look like stairs not a flat line downwards. So it’s all good!

 

[Calm Logic]

What concerns me the most about stacking tirz with reta during a transition would be reta's glucagon receptor (GCGR) activation, since that is completely unknown to me as a tirz user:

Stacking GLP1 peptides isn't exactly like 1+2=3, so my suggestion would be trying something non-GLP such as cagri (amylin analogue) or tesa (growth hormone releasing hormone)

If you stack Reta with tirz, then you're upsetting the carefully designed agonist ratio of each one.

If you want to switch up the glp1 you're taking, my suggestion would be Reta solo, since you're already considering it, because it is aa beast!

Potential for Unforeseen Effects:

• Glucose Homeostasis: While retatrutide's overall effect is to improve glycemic control and reduce blood sugar, the GCGR activation could transiently increase glucose production. However, the strong GLP-1 and GIP agonism would likely counteract this, leading to a net glucose-lowering effect. Still, for someone already on tirzepatide, understanding this delicate balance would be important.
  
  
• Side Effects: Glucagon receptor activation can potentially lead to some side effects, such as increased heart rate. While clinical trials of retatrutide have reported a safety profile similar to other incretin-based therapies with common gastrointestinal side effects (nausea, vomiting, diarrhea), the combination could theoretically alter the frequency or severity of these or introduce new ones.
  
  
• Individual Variability: How each individual responds to GCGR activation, especially in combination with existing GLP-1/GIP agonism from tirzepatide, can vary.

OTOH, plenty of people who have type-2 diabetes are on at least several medications that work in different ways. And I never heard of anyone being in the hospital from stacking reta with tirz, including some people who start at higher doses of reta. But reta is experimental itself.

For heart rate monitoring, I use my Fitbit. But, ideally, when doing any experimental, I would also be doing continuous glucose monitoring or at least daily blood sugar checks.

On the positive side:

It's the best thing I could have done! I have my life energy back, no more exhaustion, no more constant headache, I can look at food without revulsion, while the fat continues to melt off, even after a day of indulgence (as much as one are able to on a glp-1).

When I wanted to switched over I had the same questions as you. Everybody told me how cautious I should be, I got advice such as, first titrate down, start at the bottom again, even suggesting super low starting dosages such as 0.5mg, because of "how strong it is". Double stack low doses with tirz at first, cause you know - "the dreaded food noise will come back on reta!"

At that point I was on 5mg tirz. I decided to throw caution to the wind, and started reta on a conservative higher low dose of 2.5mg (my supplier uses the same dosage protocol as tirz), and waited for this "terrible strong glucagon to create havoc on my body" - nothing! I felt great! The next week I went up to 5mg, and I still felt great. I worried for nothing, I probably would have been fine going straight over to 5mg reta as well.

I don't have food noise on reta, I have the same suppression I had on tirz, I can eat just as little on reta as I could on tirz, I stay full just as long as I did on tirz - but I have more life energy, and that's EVERYTHING. I should have started on reta, like I initially wanted to, and not listened to the "always start at the bottom glp-1" crowd.

Good luck!

Having stacked Tirz, Cagri and Reta, if food noise is annoying you, add Cagri. Low doses can reduce the food craving or completely stop you from eating altogether. Works wonder for me as I am at max dose for Tirz.

Im on 6mg reta and 5mg tirz and 1mg sema weekly.

Reta 3mg twice a week.
Tirz stacked on another day.
Sema for food noise.

Everyone is different, see what works for you.

Reta at low doses doesn't have as good appetite suppression. But, I love the active fat burning. I would, and have, stacked Tirz and Reta. Reports are that when you hit 6mg of Reta and above the appetite suppression kicks in and you can transition fully to Reta. I took a different route that worked for me, but I'm just experimenting. I went all the way up to 15mg on Tirz and slowly titrated up to 5mg on Reta. The appetite suppression was so strong I could only stand it for 2 weeks. I then started titrating down on Tirz and up on Reta. I'm currently at 12mg Reta and 4mg Tirz. Honestly, I think I could stop the Tirz, but I have so much of it that I am continuing to use it in small amounts. I may drop the Tirz to 2mg in the near future if the Reta continues to give me strong appetite suppression. By the way, the only real side effects I had was when I went from 5mg Tirz to 7.5mg Tirz (massive fatigue for 2 days), and when I jumped from 1mg Reta to 3mg Reta (diarrhea for a week).

I’m currently stacking Tirz 10mg and Reta 2mg. Almost zero “food noise” and the weight is definitely coming off. I’ve been reading a little about Cagrilintide and how it affects different receptors than the GLP/GIP’s but is supposed to work great with Sema. I’ve been trying to find out if it is ok to stack with Tirz or Reta to find the best combinations.

Used to do Triz+Cargi and then Reta+Cargi 4 days later, but its just to much injecting at the end of the week.

Triz/Survo is more convenient....

Tirz 7.5 + Cagri .5 same day and Reta 4mg + Cagri .5mg same day. I dose every 3 days alternating stacks

May I recommend Survo..

My stack was 7.5 Tirz, 1mg Cagri, & 4mg Reta.

Cagri helped the suppression for the last 4 or 5 weeks . Reta helped those last lbs MELT off

But like you, Cagri kicked my ass in terms of fatigue. Personally anything more than the .5mg dose is a no go for me and it stopped being helpful. Cagri might be great to cycle.

I ended up dropping my beloved Tirz and stopped the Cagri... Added starter dose of Survo .6mg and it's my new favorite. Suppression is amazing even 4 days post 1st injection.

Frontiers | Role of Glucagon and Its Receptor in the Pathogenesis of Diabetes

Various theories for the hormonal basis of diabetes have been proposed and debated over the past few decades. Insulin insufficiency was previously regarded a...

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