Advice on transitioning from Sema to Reta?

[Cgrey80]

I'm a longtime weekly sema (Wegovy) user -- for about 18 mos. I take it primarily for insulin resistance -- and it's been great in that regard.

Unlike most folks with GLPs, I don't seek major appetite suppression. Been at a weekly maintenance dose of 1mg/week for a year. Insurance is no longer covering, so I'm using opportunity to trial Reta instead.

Thoughts on whether I should do my first Reta dose also at the same 1mg as the Wegovy or should I start lower? Definitely don't see myself starting higher as I already have a smaller appetite and don't want to decrease it further. But, will take the other fat loss benefits for sure — want to drop another 5-7% body fat over the next year.

Appreciate any insights on making the transition.

 

[Calm Logic]

I would avoid stacking together on the same day, especially for the first time. I usually wait at least two to four days between GLPs when doing any significant dosing or if using something new. Even GLPs with a shorter half-life like liraglutide may have upper and lower GI effects a few days down the line.

Another option is to split the dose, so 0.5 mg of reta the same day as Wegovy/sema and then, based on how you are doing, another 0.5 mg of reta again later in the week.

 

[Cgrey80]

I would avoid stacking together on the same day, especially for the first time. I usually wait at least two to four days between GLPs when doing any significant dosing or if using something new. Even GLPs with a shorter half-life like liraglutide may have upper and lower GI effects a few days down the line.

Sorry, I guess this wasn't clear. This wasn't about stacking. I have no intention of stacking. This is about discontinuing Sema and transitioning to Reta instead.

 

[Calm Logic]

Sounds good to me. But it's possible even 1 mg of reta will hit you a little hard. You never know, especially since you already have a smaller appetite and the sema already in your system can have some effect for several weeks or so.

So to be really safe, one could start reta at 0.5 mg twice a week (for the first week anyway). Another reason to spread out reta the first week is that the first dose is ideally a baby dose when trying a kit for the first time.

 

[BellyD]

I'm slowly moving from Triz to Reta, then Plan to use SEMA with Reta for ap suppression.
Go slow, I started with 2mg of Reta, Twice a week. Then have moved to 4.5/5mg once a week after.
Currently on 5mg of Triz and 5mg of Reta.

Also note, there's a lot of vendors who overfill. So take that into account. Typically by 5-10%>
I have 15mg vials that measure from 15-18.

 

[Calm Logic]

No sides with 4 mg total the first week? I get sides with 2 mg as I am more sensitive lately, and I don't know why (possibly from switching things around too often, or having taken a month off GLPs earlier due to traveling/chaos but gained no weight).

I have contributed to the bad rap reta gets for suppression. But when I tried it again (without stacking), 2 mg hit me like 5+ mg of tirz. So I don't know what to think, except it depends on your body that day/week/month, haha. It was also a different vendor, but I don't think that was the issue.

 

[YoYoFat]

Sorry, I guess this wasn't clear. This wasn't about stacking. I have no intention of stacking. This is about discontinuing Sema and transitioning to Reta instead.

Transition usually involves stacking during the period of transition.

 

[Calm Logic]

From Gemini:

Common transition strategies include:

Washout Period: Stopping Sema entirely and waiting 1-2 weeks before starting Reta.

Direct Switch: Stopping Sema on the usual injection day and starting Reta on the next scheduled injection day (less common due to half-lives).

Tapered/Overlap: Temporarily taking the last Sema dose at the same time a low Reta dose is started, which is a form of brief stacking to maintain stable drug levels.

The prescribing doctor will determine the safest way to transition, which usually involves:

Option 1 (Common): Completing the last Semaglutide dose, waiting a specific number of days (the washout), and then starting Retatrutide at its lowest starting dose (e.g., 1mg or 2mg), followed by the normal slow titration.

Option 2 (Less Common/Specific): A very brief, low-dose overlap (what your interlocutor called "stacking") to ensure drug levels don't drop too low, followed immediately by the Reta titration.

 

[Cgrey80]

Transition usually involves stacking during the period of transition.

I see. In my case my sema is the official Wegovy and I can't adjust its dose. It's an all or nothing style pen, so I wouldn't be able to follow that type of transition protocol that would work for those transitioning From a vial-based sema to a vial-based Reta.

I think I'll start week of Reta at 0.5mg (after a brief wash-out) and see how it compares to my 1mg sema dose I've been on.

 

[YoYoFat]

From Gemini:

Is there a reason you never quote people and just appear to passive aggressively respond to someone above you?

Gemini isnt correct here, IMO. It’s not just the very last dose that’s stacked, it’s a period of a few to several weeks, depending on the dose of the current pep. One week might be enough if they were only using .25 Sema, but not a midrange dose like OP is on.

 

[YoYoFat]

I see. In my case my sema is the official Wegovy and I can't adjust its dose. It's an all or nothing style pen, so I wouldn't be able to follow that type of transition protocol that would work for those transitioning From a vial-based sema to a vial-based Reta.

I think I'll start week of Reta at 0.5mg (after a brief wash-out) and see how it compares to my 1mg sema dose I've been on.

You could recon your pens into vials and draw from that. Many people do that to adjust doses.

 

[Cgrey80]

You could recon your pens into vials and draw from that. Many people do that to adjust doses.

No, I don't think that's possible with a Wegovy pen. It's not like the DIY pens we use in research peptides. But, thanks!

 

[YoYoFat]

No, I don't think that's possible with a Wegovy pen. It's not like the DIY pens we use in research peptides. But, thanks!

Yes, it is possible. I did it. Lots of people do it. It’s called pen splitting, done to split the dose of a pen into smaller doses drawn from a vial.

Read this. https://www.reddit.com/r/Zepbound/s/4WzkGUfI7A

And watch this:

View: https://www.youtube.com/watch?v=9uoAZTE3PK0

 

[Calm Logic]

Gemini isnt correct here, IMO. It’s not just the very last dose that’s stacked, it’s a period of a few to several weeks, depending on the dose of the current pep. One week might be enough if they were only using .25 Sema, but not a midrange dose like OP is on.

Additionally, there was also more talk of washout periods in the past. But it seems a washout period of only one week is what most of us do anyway, with the last dose of the old GLP being a week ago:

Washout Periods Explained: Switching Safely Between Weight Loss…

readyhealth.co.uk

 

[Cgrey80]

Yes, it is possible. I did it. Lots of people do it. It’s called pen splitting, done to split the dose of a pen into smaller doses drawn from a vial.

Read this. https://www.reddit.com/r/Zepbound/s/4WzkGUfI7A

And watch this:

View: https://www.youtube.com/watch?v=9uoAZTE3PK0

Interesting. TBH, I appreciate it but I don't see myself doing that. I wear a CGM, I closely monitor my side fx, I have regular labs every six weeks. I think I'm comfortable with a cold break from the Wegovy.

 

[YoYoFat]

Interesting. TBH, I appreciate it but I don't see myself doing that. I wear a CGM, I closely monitor my side fx, I have regular labs every six weeks. I think I'm comfortable with a cold break from the Wegovy.

Not sure the CGM or labs have anything to do with whether to stack or go cold when switching. The point of stacking in transition is to limit/eliminate sides.

Since you’re the expert and apparently didn’t even need to post this thread, I’ll leave you to it.

 

[tubby]

Here is what a true cold break would entail:

If you're on weekly 1mg doses, that means your body levels are fluctuating between 2mg (max level on shot day) down to 1mg (the remaining dose in your system 7 days later).

If you went 14 days between your last sema and your first reta dose, you'd still have 0.5 mg of sema in your body when you started reta.
At 21 days, that would be 0.25mg...

 

[Cgrey80]

Not sure the CGM or labs have anything to do with whether to stack or go cold when switching. The point of stacking in transition is to limit/eliminate sides.

Since you’re the expert and apparently didn’t even need to post this thread, I’ll leave you to it.

I'll be generous of spirit and just assume emotional reactiveness is a side effect of whatever protocol you're on.

I told you I appreciated the education on the auto injector pen splitting. And I meant it. But proffering a suggestion doesn't obligate the questioner to adopt it. I've weighed the risk reward and don't see major benefit to that process.

The main thing I was trying to get out of this thread was an understanding of like doses between the GLPs. We're all working in a grey area here and have to assume some risk. Given my tolerance and longtime use of sema, I'm going to assume that risk by diving into a low dose of reta after a brief washout. And if I have a a headache or GI issues I can adjust.

 

[Cgrey80]

Here is what a true cold break would entail:

If you're on weekly 1mg doses, that means your body levels are fluctuating between 2mg (max level on shot day) down to 1mg (the remaining dose in your system 7 days later).

If you went 14 days between your last sema and your first reta dose, you'd still have 0.5 mg of sema in your body when you started reta.
At 21 days, that would be 0.25mg...

Thanks! That's super helpful!

 

[Calm Logic]

Definitely don't see myself starting higher as I already have a smaller appetite and don't want to decrease it further.

I really like protein drinks, especially for hydrating in the AM or if I get a little too much or too little suppression. They are filling enough when I am hungry but easy on my stomach in any case. (Everyone talks about them but for good reason. Boost, Fairlife and the Fairlife knockoff are my faves for taste. Boost has more carbs/sugar.)

I am definitely trying sema again next year, at least for stacking. The generic drug makers in India are working on it. And my supplier in India says he will be reselling the pens when they are made available.

 

[tubby]

I think the biggest conceptual challenge is probably understanding that reta is fundamentally different from sema. Both act as GLP-1 agonists (which often is described as suppressing appetite). With sema the playbook seems to be to view obesity as nothing more than an excess calorie problem with the solution being to restrict calories. There is a slight hormonal enhancement there as well, but the lion's share of the work is being done by the reduced food intake.

With reta, that effect is still present (for better or worse), but the glucagon suppression is an entirely different and independent effect that's harder to explain and perhaps not well understood. It's unfortunate that there isn't a well-studied peptide that acts only as a glucagon receptor agonist (so that this effect could be better isolated and experienced).

I might be able to offer some insight from the low-carb world (in the context of someone not taking any weight loss meds): Typically when a person eats a mixed diet (that includes high-glycemic carbs), they'll get regular hunger pings before meals. When someone goes low-carb or keto they'll often note that the volume of those pings gets turned way down, to the point where if they're wrapped up in a task they might simply forget to eat. I would wager that one of the factors at play here is a both lower and stable glucagon level on low-carb and suspect that as glucagon creeps back up (when not on low-carb), that's one of the hunger triggers. To the extent reta keeps glucagon from creeping back up at those points, it should to some degree simulate the appetite suppression effects associated with low-carb diets. Just guessing here, of course.

 

[Calm Logic]

@tubby Thanks, so I may not have to stack much, if at all. A reiteration with a minor clarification:

You are completely right that Retatrutide simulates the "metabolic silence" of a low-carb diet. But it does so by mimicking the high-glucagon signaling of keto, not by suppressing it. It convinces your body that it is currently mobilizing massive amounts of fat, and therefore, it doesn't need to ask you for food.

 

[tubby]

@tubby Thanks, I may not have to stack much after all, though some do. A clarification:

I'd be interested in the logical progression it went through to reach that conclusion, as it seems faulty, although I certainly could be mistaken too.

The glucagon-agonist in reta is increasing glucagon signaling at receptors (making your body think there's tons of glucagon, when in reality there is not). Through some pathway or another this is causing the pancreas to release less glucagon (after all, if there's plenty in circulation why would it want to release more). The net result is lower glucagon levels in the blood.

I guess the mystery here is whether the part of the brain creating "metabolic silence" in response to the false high-glucagon signal (from the receptors affected by the the agonist) or if it's reading a low-glucagon signal (as actually exists in the body). I guess both could be reasonable answers, since I suspect it's really the CHANGE in glucagon levels (as you transition between fasted and fed states) that's what actually being detected. After all, if you're on a mixed macro diet (with no drugs) and skip a meal, the strong hunger sensation does usually start to decrease again after 30 minutes to a couple of hours if you don't eat.

 

[Calm Logic]

Gemini: "It is easy to blame the glucagon because it is present during the hunger pangs. But glucagon is the ambulance, not the car crash. The crash (low blood sugar) caused the hunger; the glucagon was just trying to stabilize you."

 

[tubby]

Gemini: "It is easy to blame the glucagon because it is present during the hunger pangs. But glucagon is the ambulance, not the car crash. The crash (low blood sugar) caused the hunger; the glucagon was just trying to stabilize you."

That just doesn't make any sense. If someone eats a mixed macro meal at 12PM, their blood sugar bumps up about an hour after the meal and comes back down to baseline within 1-2 hours after that. The hunger sensation occurs several hours after that (at which point blood sugar has been stable, but glucagon has been rising).

If there was a blood sugar crash, that would have happened 1-2 hours after the meal and Gemini's response would make sense for explaining hunger in that timeframe.

 

[Calm Logic]

Thanks, and sorry, it was missing the forest for the trees:

I usually double check Gemini before posting, but glucagon is still new to me.

I had a bit of ketones during my urinalysis last week, so that was my own focus:

Medication	Mechanism of Action	Glucagon Receptor Effect	Likelihood of Ketonuria
Retatrutide	Triple Agonist (GLP-1, GIP, Glucagon)	Agonist (Actively Stimulates)	Highest (Directly promotes fat-burning/ketogenesis)
Tirzepatide	Dual Agonist (GLP-1, GIP)	Indirectly Suppressive (GLP-1 component)	Low to Moderate (Only from severe calorie deficit)
Semaglutide	Single Agonist (GLP-1)	Indirectly Suppressive (GLP-1 component)	Lowest (Only from severe calorie deficit)

 

[tubby]

Thanks, and sorry, it was missing the forest for the trees:
View attachment 11442
I usually double check Gemini before posting, but glucagon is still new to me.

I had a bit of ketones during my urinalysis last week, so that was my own focus:

Don't sweat it. I appreciate you trying to push back, since it's easy to get caught in your own world of confirmation bias and critical responses helps me avoid that.

Sadly, I think LLMs aren't going to be reliable when it comes to this, but they could be worth using as a starting point. That's in part because I'm not sure sure if a lot of high-quality research has been done on this stuff since the 1970s and also because everything in biochemistry is so intertwined that unraveling cause and effect isn't as straightforward as one might desire. Cholesterol is a great example of this, where we still don't have a coherent story in regards to what it actually means and that's something that's very highly researched.

 

[tubby]

Thanks, and sorry, it was missing the forest for the trees:
View attachment 11442
I usually double check Gemini before posting, but glucagon is still new to me.

I had a bit of ketones during my urinalysis last week, so that was my own focus:

Interesting they would check ketones in the urine. I guess it could make sense if someone presented with diabetic symptoms and they wanted to rule out ketoacidosis. Otherwise, ketone levels in urine is a pretty worthless metric since it doesn't correlate well to ketone blood levels, which is a much more useful metric.

 

[BellyD]

No sides with 4 mg total the first week? I get sides with 2 mg as I am more sensitive lately, and I don't know why (possibly from switching things around too often, or having taken a month off GLPs earlier due to traveling/chaos but gained no weight).

I have contributed to the bad rap reta gets for suppression. But when I tried it again (without stacking), 2 mg hit me like 5+ mg of tirz. So I don't know what to think, except it depends on your body that day/week/month, haha. It was also a different vendor, but I don't think that was the issue.

I have side effects only if I add Triz as my second shoot. Typically GI. Triz then reta is fine for me. Its completely possible my titration schedule is off due to those effects. As far as vendor I have CHP Reta (15) and Jeep (30) triz. For my 🐀
I will note, I'm looking at these slight overflows with a keen eye. As I'll be shooting for a 8mg Reta dose per week. So I'll need 32mg+ vials per month.