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Big Picture Reta Questions

BioDad

GLP-1 Novice
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I have a couple of questions about reta that have been bugging me.

Quick background - I'm a total newbie to this, only about 5 weeks into reta, and literally never touched any other peptides before. Yeah, I know, pretty vanilla.

So I've been digging around trying to understand a few things that don't quite add up for me:

First thing - I keep seeing people swear by once-weekly dosing, saying it's better and more efficacious than splitting doses. But honestly? This doesn't really track when you look at the pharmacokinetics. I get why the trials did weekly dosing (convenience for participants, plus the ~6 day half-life makes it practical), but I'm struggling to understand why it would actually be more effective than splitting. There's a clear threshold dose, similar to most medications, that is required for it to have an effect, but that seems to at least be around 2mg, so anything beyond that is likely enough.

If doses are split, there would be smaller peaks and troughs but the same average levels over the week (eg, lower Cmax, higher Cmin, same Cavg/AUC). The only explanation I can come up with is that people "feel" it working more with the big weekly dose because they get that strong appetite suppression hit at the start of the week (along with more side effects), but then it tapers off by day 6-7. Am I missing something here? I understand the experiences of people and people swear by both sides of the argument, but scientifically, I'm trying to rationalize how once a weeks is possibly more efficacious than split doses. (For the record, I'm using split doses and am quite happy with it, but am willing to do whatever has a better impact.)

Second - This one's been really puzzling me. I've seen loads of people who've used sema or tirz saying they were hungrier and with more food noise than while on reta and end up switching back to tirz, or stack both. I understand that everyone responds differently, but here's what I don't understand...

All the reta studies show pretty impressive weight loss WITHOUT any special diet/exercise programs. Just the medication alone. So presumably those trial participants had normal hunger cues like the rest of us while on reta. =Yet, they lost a considerable amount of weight.

My theory is that even if reta gives you more hunger and less satiety compared to tirz, if you 1) stick with a high enough dose for 2) enough time, you'll 3) likely get the weight loss results, despite stronger hunger cues. At least that's what the studies seem to show. Again, personally, I still get hungry on reta, at the same times of day as previously, but end up eating one serving of dinner rather than two, and sweets have zero appeal at all now (Eg, the KitKat bar while checking out at Walmart). It has just taken the edge off, which I quite like so far.

Does anyone have insights on either of these? Thanks, and I hope everyone enjoys their weekend.
 
On tirz I get full after a few bites and get hungry less often. Appetite suppression.

On reta the appetite suppression seems to be less, I feel latent hunger, empty feeling, then wander to the fridge and nothing looks good, so I don't eat anything.

Someone else said tirz suppresses your appetite while reta turns you off to food.

I can't explain why this is, and it does seem like tirz is more potent, but as you said, reta gets better results in trials. No idea
 
I’ve heard it described as Tirz is a patch and Reta is a repair. Like theoretically after some time you can stop Reta and it will have rebalanced your hormones and regulated your system. Whereas Sema/Tirz are lifetime drugs… but that was only from some crazy TikTok chiropractors so I don’t know if I believe it.

You could try to theoretically match the peak serum levels at 6day half life via daily injections. For example following the 2mg weeks 1-4, 4mg week 5-8, 8mg week 9-?? Titration schedule of the RCT you could do 0.6mg daily weeks 1-4, 1.2mg daily weeks 5-8, then 1.8mg daily weeks 9-??

I think that daily schedule makes a few assumptions about metabolism curves that might not be accurate. If you want the results of the study, follow the study protocol. If you change up the protocol, expect different results. Let us know how it goes with whatever protocol you choose to research. You could be onto something.
 
I look at the dosing schedule like my (former) drinking schedule. If you want to get drunk (maximum weight loss) do you drink a shot every few days or several at once?

Then you factor in old school thinking in nutrition and dieting. Is there truth in tricking the body out of starvation mode by varying your consumption from intermittent fasting and indulgence? Basically this is the way most people report their appetite on a 7 day dosing routine.

It's unfortunate the amount of people trying to shut off hunger entirely with GLPs. We're not robots and those are the people who titrate too quickly stack and burn through all their options.

Personally I like feeling the effects of my GLP and dosing once per week I feel it heavy on the front end, on the back end I eat more. It worked at 5mg to goal (5mg Tirz). No diet, no exercise, no scale... just patience. I know that's unique but I also know the scale has been a trap and a source of PTSD and I would have titrated higher/faster with bad scale days. (-75lbs/10mos)

As to your Reta observations we have to remember study participants are not stacking or exercising gray options. People in the forum have a buffet of options and I can speak for many of us our penchant in navigating a buffet! There's a spectrum of goals here where Sema and Tirz emphasize weightloss whereas Reta brings in people who may want the weightloss but also people from the fitness realm. You see the word "cut" in relation to Reta with a frequency I've never seen it with other GLPs
 
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All the reta studies show pretty impressive weight loss WITHOUT any special diet/exercise programs. Just the medication alone. So presumably those trial participants had normal hunger cues like the rest of us while on reta. =Yet, they lost a considerable amount of weight.

Almost everyone reports lessened hunger on reta, that does not seem like normal hunger cues to me.
 
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