Split vs Single dose- how many mg?

[RetCurious]

I split it at first thinking that was superior and researched the heck out of it, even contacting lead researchers on major papers on retatrutide. I was convinced it was a superior way and the once-a-week dosing in research was more out of convenience than it was pharmacodynamics/kinetics.

I've since changed my tune and now do a once weekly schedule. Not only is that only what has been researched, but - I'd have to dig up my notes on it as it was a couple of months ago - what ended up convincing me was the steady decline throughout the week might actually result in it working a little better from a receptor point of view. If I recall, there was a paper on Semaglutide that tipped my scales on that but again, I'd have to dig it up.

I'd be interested in reading that paper, thanks.

 

[Fat2Fit26]

Update on my personal journey as of this sub.

Switched to a 2mg dose schedule Monday & Thursday as of today. Let’s see how that feels for a few weeks.

 

[Phatmax]

i used to split on monday and thursday but ive found better results with one shot of 4mg every 6 days

 

[DazDillinger]

I do Reta every other day it’s just what I like best and it worked for me have done everything from .5mg every other day to 3.5mg only issue at the higher dose was some skin sensitivity and feeling cold but wasn’t bad enough to have to drop.

 

[SeaGypsy]

Update on my personal journey as of this sub.

Switched to a 2mg dose schedule Monday & Thursday as of today. Let’s see how that feels for a few weeks.

Let us know how it works for you, I have been considering split dose, I start getting alot of food noise around day 5

 

[woundcarping]

Hey Woundcarping. I’m here to learn. It wasn’t a statement of fact, just how I currently understand it. Would be great if you could clear up the math for me so I have a better understanding.

Thanks!

It took me a minute to make time while sitting at a keyboard so I could type easier.

I'm leaning more to the math side of things and pharmacokinetics and less into the pharmacodynamics.

Reta's 6 day half life is touted on social media like it's a cornerstone of efficacy... it's just a simple approximation of how long it takes half of the compound to be eliminated from our system. Getting closer to a week makes dosing schedule adherence easier for the customers, ie pin once a week and be bless with all you hope for. It also allows accumulation of levels... it's not meaningless, but it's not the Holy Grail.

As you said, there's a delay (Tmax) from injection to peak levels (Cmax) in the system and the half life (T1/2) means half of the dose will be gone in that period of time. I assume/use 24 hours, mainly because that roughly matches the app I use to track my levels, it's at least somewhat based on scientific data, and my observations don't disagree with that approximation.

You can also model that the injected dose starts being eliminated as it's absorbed, which skews the peaks lower and is probably more accurate than not including that elimination. That's part of why a dose given doesn't boost your levels by the amount administered.

I split dose, 2x weekly, which keeps the scheduling simple. I don't normally concern myself with getting it dead nuts 3.5 days because I haven't found it matters. When I started on Tirz, I soon realized around day 5 my appetite and food noise was back. Given the 24 hour absorption window, I like to forecast my needs at least that far ahead to make sure I'm covered, vs waiting for an issue to present and the solution is a day away... it's not that serious, but it's easy to plan around.

With it having a half life of 6 days seems potentially excessive to split the dose no? Maximum concentration is said to be 12-72 hours so you’re re-dosing then at max concentration.

This is where you had the components of the math, but they weren't applied correctly... peaks come a day after injection.

If we assume 24 hour Tmax, 6 day half life, 8% eliminated during Tmax.
Day 0 First injection administered.
Day 1 First injection peaks
Day 3 27% of the first injection has been eliminated, second injection administered
Day 4 35% of the first injection has been eliminated, second injection peaks.

So when the second dose peaks, the first dose only has 65% remaining, and ~8% of the second dose was eliminated during Tmax.

Maybe re-dosing on day 5 or 6 may make more sense if feeling a lot of food noise, hunger and cravings towards day 6/7. Although understand that’s harder to keep track with the day moving each week.

I don't think a 5-6 day schedule is "wrong", it is more hassle than I want. With my desire to plan ahead for symptoms (namely food noise) and the 24 hour Tmax, I favor twice a week.


Peaks drive symptoms, troughs determine efficacy. Average exposure is the same, regardless of splitting or not. Peaks get suppressed and troughs lifted through splitting. Receptor burnout is something I don't have a strong position on, either way. Split dosing can result in a lower weekly exposure with the same efficacy through suppressed peak and trough variations... perhaps favorable to receptors through less total load. Or, the lack of variation can cause more burnout because they don't have times at lower concentrations... but the average is still the same.





With other things, like testosterone cypionate (T1/2 of 8 days), split weekly dosing tends to strongly lower adverse side effects once weekly or every other week injections. Same average exposure, suppressed peaks and troughs, better results (with some nuances/caveats).

 

[Nopenada]

Pretty new to Reta so still figuring this out.

I started my first couple of weeks on 1mg; at .5mg twice a week just to ensure I wasn’t going to have some of the nastier side effects from the get go.

Then switched to 1mg once a week. Pinning Mondays. So far I’ve found that starting Friday morning it has worn off from a food noise standpoint, but still not the best sleep even after it wore off and I usually sleep like a baby.

I let myself eat everything in site over the weekend. (It was the Super Bowl!) But the scale was still down on Monday, which was nice.

I don’t have a lot to lose and would rather do it slowly for look skin reasons. I’m on the fence if I’ll split the dose and maybe try .75 twice a week or if I’ll hold at what I’m doing now and let my self eat and drink on weekends.

From a sleep standpoint I may just adjust or my plan on adding Tesa/Ipa might make a difference.

 

[bogardbilla]

I see people jumping through hoops, doing cartwheels and amateur scientific research around half-life, blood levels of GLP-1 etc. but when you look at it from a distance it's all actually in the effort to rationalize and justify their fear of getting some of their appetite and food noise back.

I personally do a shot every 7 days precisely because I want to feel hungry a little bit for a day or two in a week. I don't think having my receptors flooded with GLP-1 24/7 is a good idea either short or long-term.

 

[neo6488]

I see people jumping through hoops, doing cartwheels and amateur scientific research around half-life, blood levels of GLP-1 etc. but when you look at it from a distance it's all actually in the effort to rationalize and justify their fear of getting some of their appetite and food noise back.

I personally do a shot every 7 days precisely because I want to feel hungry a little bit for a day or two in a week. I don't think having my receptors flooded with GLP-1 24/7 is a good idea either short or long-term.

I mean yeah. Why else are we doing this if not to feel hungry?

I would rather push through quickly and get to a maintenance phase than drag the weight loss out.

 

[bogardbilla]

I mean yeah. Why else are we doing this if not to feel hungry?

I would rather push through quickly and get to a maintenance phase than drag the weight loss out.

I'm not sure if never feeling hungry correlates with losing weight faster. I've lost 63 lbs in 20 weeks doing my thing.

 

[ftv10hb]

I started out 3x/week, at first dosing 1mg each pin, then 1.5, then 2mg. I never asked when or how I was supposed to transition to 1x/week, and everything was working great, so I just kept going at 2mg 3x/week. This was before I’d bothered to learn anything about half-life or other information I have now, and it wasn’t long before I ended up with a recent case of the skin sensitivity others have mentioned. It wasn’t brutal or anything but also wasn’t enjoyable at all lol. I had to travel for a few weeks and didn’t dose at all so kind of ran into a natural reset. The allodynia went away as the drug cleared out of my system. Now starting again I am definitely making use of the glp plotter to compare how much is in my system with how I feel at that point. The idea being to find a generally consistent level at which my food noise is minimized but side effects are mostly avoided or tolerable.

Everyone is going to be different as far as as effective dose levels, hunger/food noise, goals, and side effects, so I think at the end of the day the number of times you choose to pin each week is going to depend on your own preferences and experiences. My advice would just be to make sure you are tracking your dosing on a plotter so that if you do run into food noise or an unpleasant side effect, you can look at that and say ok I need to make sure my levels stay above this point or below that point, and then create a dosing schedule that works for you based off actual tracked numbers instead of just the feels.

 

[Main75]

Okay just to open a can of worms, who is splitting their doses and who is going singular ? How many mg’s are you up to ?

I have previously split my dose and feel that there isn't as many highs and lows, but I am on the singular route for convenience.

Im up to 4mg and looking at the clinical trials there isnt much difference from 6mg just more side effects.

Back to you ?

My understanding is its about the build up in your system for GLP-1 (semi, triz, reta ) all having half lives of about a week.
this may be redundant info
Example:
-Dose 1 MG at start of the week by the end it is only .5 active
-Dose 2 1MG at start of week plus the .5 left from week one (1.5mg active ) byt the end of the week you will have half of the week 2 dose active ( .5mg) and half of the half from week 1 dose active so ( .25mg )
-Dose 3 1mg start of the week totals 1.75mg active .....blah blah
*not need to consider after 4 week

Consideration for reta has another element Glucagon which kicks in over a certain dose 4-6mg (not certain if this differs in different people. so why could this matter ?
If you split doses and baseline medication load does not get higher then the Glucagon receptor element that is unique to reta may not be as activated.

The flipside argument:
Separating doses is like "sipping' rather then gulping the same amount and could make getting used to increased doses less of an issue if you are prone to or already having side effect issues

At least that how i have envisioned it

 

[Speak_Easy]

Okay just to open a can of worms, who is splitting their doses and who is going singular ? How many mg’s are you up to ?

I have previously split my dose and feel that there isn't as many highs and lows, but I am on the singular route for convenience.

Im up to 4mg and looking at the clinical trials there isnt much difference from 6mg just more side effects.

Back to you ?

I'm interested in this. I'm doing 3.5 of R after 3 months 5 of T and I get stomach acid for 24 hours after each 3.5 dose. I'm going upon to 4 this week and considering splitting 2 on Thursday and 2 on Sunday to see if this stomach acid stops.

 

[Thadeus]

I've been having good success splitting the recommended dose in half every 3 days. No significant sides and the weight is falling off.