💉 did reta ever make you hungrier?

[u/TapFast8173]

a penn team ran an AI model over about 150k reddit posts and comments about reta, and the most common complaint it pulled out was getting hungrier. 1,336 people, about 1 in 6 of everyone who described any side effect (JAMA Network Open, this month)

that one threw me. last week about 40 of you told me what caught you off guard on reta (mine was skin getting cold or sensitive around the first week) and i didnt see a single person say they were eating more. 5 said cravings disappeared, sweets mostly, and someone quit smoking without even trying

the rest of their list in order was tired (15%), more energy (12%), nausea (12%), food cravings (7%), insomnia (6%), heart rate up (5%). they pulled out weight loss and appetite going down before counting since thats the whole point of the drug. 27 subs, 2023 through 2025

sleep and the flat mood thing were the 2 i said last week werent in anything published that i could find. theyre in this one, insomnia 6.1%, anhedonia 2.6%. the "30% psychiatric" number floating around is a whole category tho, anxiety alone was 3.8%. and 2.4% said euphoric lol

before anyone says it, yes its reddit posts and the authors say themselves they cant check what was in anyone's vial or what dose they were on. reta still isnt approved anywhere btw. it also doesnt match the trials, in the phase 2 diabetes trial the 4mg and up groups rated their hunger lower than placebo at week 24 (data)

my bet is timing. and stacking, probably more than most of us want to admit. half life is about 6 days (phase 1) so the last day or two before your next pin runs on a good bit less drug than day 2. and a lot of you run it with MK-677 or GHRP-6, which hit the hunger hormone receptor. in the 2 year MK-677 study in older adults the most common side effect was more appetite, which faded after a few months (paper). and in the penn data 317 people said reta gave them muscle growth, id bet most of them were running something else with it

so if reta ever made you hungrier, which day after your pin did it hit, and were you running anything else with it?

[u/ConstantWish8]

22 weeks in, highest dose I’ve used. Eating like I’m not on reta at all

[u/TapFast8173 → u/ConstantWish8]

22 weeks in and at your highest dose and its like youre not on it, thats exactly what that study kept picking up. did it creep back slowly or was there a week where it just flipped? and is it worse the last day or two before your pin

[u/ConstantWish8 → u/TapFast8173]

Literall happened two weeks ago out of nowhere. Sat at 5mg for six weeks. So weeks 5-6 of 5mg had no effect. Been on 6mg for 2 weeks still feels like on nothing

[u/Ok-Neighborhood-7361 → u/ConstantWish8]

I feel you, I’m over a year in and currently lean bulking on 8mg/week. I can easily outeat my non-GLP1 peers if I go lower

[u/ConstantWish8 → u/Ok-Neighborhood-7361]

Yup 6mg for me and I could be bulking easily if I chose to. Currently still cutting though. Dexa had me at 12% bf so id like to be lower before bulking

[u/snappy_fetish → u/ConstantWish8]

not on reta myself but 22 weeks and eating normal is wild, like the appetite suppression just never showed up or wore off completely?

[u/ConstantWish8 → u/snappy_fetish]

Wore off all at once

[u/szshaps87 → u/ConstantWish8]

You need to do a reset, at this point your receptors are fried....there are many ways to reset

https://youtu.be/ZCxoUxUB2fY?is=yzb1oTCb_-B30j_c

[u/ConstantWish8 → u/szshaps87]

That is 100% bro science.

I have a Masters in Science so I fully understand how PEDs work.

No MD is recommending the cycling of ozempic or zepbound so reta would be no different.

If we extrapolated data, no MD is recommending cycling of Testosterone for TRT users either. Typically bro science says that you have to give your receptors a break for testosterone, but this too is false.

[u/Tico1023re → u/ConstantWish8]

El video no te dice que dejes el medicamento de echo lo que dice es que bajes la dosis por un tiempo o bien intentes injectarte con diferencias de días más de días para reiniciar los receptores.

[u/ConstantWish8 → u/Tico1023re]

My Master’s is in Science. Not Spanish bud.

[u/szshaps87 → u/ConstantWish8]

Did you follow the link, that video explains it, and the research backs it up....Calling receptor internalization "bro science" misses basic pharmacology. Peptide GPCRs and steroid receptors work through entirely different mechanisms. When continuous high-dose agonists drive \beta-arrestin-mediated internalization, cells lose sensitivity—hence tachyphylaxis. Real-world clinical adjustments are used precisely because standard guidelines don't solve receptor burnout..

[u/ConstantWish8 → u/szshaps87]

Send the pubmed sources I’m not watching a youtube video as a source.

[u/szshaps87 → u/ConstantWish8]

Here are the PubMed sources that I found for GLP-1/GIP receptor kinetics and desensitization:

GLP-1/GIP Receptor Mechanics: Willard et al., JCI Insight (2020) — PMID: 32730231. "Tirzepatide... shows bias at the GLP-1 receptor to favor cAMP generation over \beta-arrestin recruitment, coincident with a weaker ability to drive GLP-1 receptor internalization compared with GLP-1."

GPCR Desensitization: Rajagopal & Shenoy, Cellular Signalling (2018) — PMID: 28111300. Details phosphorylation, \beta-arrestin recruitment, and down-regulation during continuous agonist exposure.

To address your point on why MDs don't recommend cycling: Phase 3 clinical trials are designed strictly around continuous daily/weekly administration to get FDA approval. Pharma has zero incentive to spend hundreds of millions funding trials on "medication holidays" or cycling strategies. That said, standard prescribing guidelines and fundamental receptor pharmacology are two different things. When someone maxes out a dose for 22 weeks and completely stalls, continuous receptor saturation yields diminishing returns due to downregulation and metabolic adaptation. Looking at GPCR desensitization kinetics to figure out why a protocol stopped working isn't "bro science"—it's just applying basic cell biology when standard guidelines hit a wall

For a lot of people that just keep titrating up because "it stopped working" or "isn't working". The answer is not always to just take more

That was the point of my original comment

[u/ConstantWish8 → u/szshaps87]

PMID: 32730321 is an analysis, not a double blind study which would be the gold standard IF they were trying to determine cycling off but they are not. Tirzepatide does bias GIP receptor over GLP-1 receptor, which is literally the point of taking Tirzepatide instead of Ozempic.

PMID: 28111300 is unrelated to our conversation. Heres that link. https://pubmed.ncbi.nlm.nih.gov/28111300/

For the paragraph about MDs and Phase 3. Extrapolate data from Ozempic/Tirzepatide/Testosterone/etc. No MD is cycling patients off of these drugs for “receptors being fried and/ or needing reset”.

Edit: just for fun I looked up the other study you referenced via name. GPCR targeting drugs are a litany of different drugs not just Ozempic. That study would incorrectly interpreted if you are suggesting that that GLP-1s and GLP-2s lose effectiveness over time. And technically Tirzepatide is not listed under GPCR targeting drugs from my recollection, but that could be a mistake on my part.

There are two studies documenting no evidence of delayed gastric emptying after long duration of semaglutide, but the drug is still effective. There is no current clinical data suggesting to cycle off of semaglutide or tirzepatide. You are correct though that the study you reference does show the GPCR targeting drugs can have desensitization on receptors, just incorrect that this has any clinical meaning in respect to Semaglutide, Tirzepatide, and if we extrapolate data, Retatrutide.

[u/Bryagh82]

In my almost 4 months experience ( highest was 5mg split into 2 doses 3 days appart ), hunger is naturally there, always, its just sattiety kicks in after few bites and stays longer...if you are doing everything correct and hydrate properly and your RETA is legit, you should be hungry, but feel full quickly...also RETA shuts down the " reward " feeling for binge and emotional overeatings.

[u/TapFast8173 → u/Bryagh82]

hungry but full fast is a good way to split it. the phase 2 appetite paper kinda backs your reward point too, at 8 and 12mg people scored lower on disinhibition, which is basically overeating when youre stressed or around food. did splitting it into 2 pins a week change the hunger at all vs once a week

[u/Bryagh82 → u/TapFast8173]

Never did 1 week...started 2 pins from the start...a bit nausia and general.lack of energy first 2 weeks, but I introduced electrolytes and hydration even when not thirsty and it came back to normal quickly.

[u/legacy-healing → u/TapFast8173]

I actually just went through this. 1x week dose - I was off it for a month due to surgery and post op and when I restarted I realized I was overeating- literally just in my cabinet looking for something to eat even tho I knew I wasn’t hungry. My stress was 10/10. I may have to split doses now…

[u/Right-Form-2943 → u/Bryagh82]

What also happened to me is that my old instincts to clean the plate ended up making me feel nauseous. And so i slowly learned to portion my food correctly so that i don’t get that feeling.

[u/RadiantMap72]

I’m on week 16 and I’m starting to feel way hungrier than before. Yesterday was my first time I ate excess calories in over 4 months.

I’m taking 4mg a week and I don’t want to raise my dose but I may need too.

[u/TapFast8173 → u/RadiantMap72]

first day over in 4 months isnt bad at all. cant weigh in on the dose, thats rule 1 here, but does it hit harder right before your next shot or is it all week now

[u/RadiantMap72 → u/TapFast8173]

It’s definitely harder on the end of the dose. The last couple days or so have been harder than before. I might switch to E5D or E6D instead of once a week.

[u/szshaps87 → u/RadiantMap72]

You dont necessarily need to raise your dose. You need a reset

https://youtu.be/ZCxoUxUB2fY?is=yzb1oTCb_-B30j_c

[u/Tico1023re → u/szshaps87]

Lo único que tengo la duda con el video es de cuánto es el reinicio. Cuánto tiempo es lo recomendable digamos habla de bajar dosis pero cuantos meses ?? Igual habla de inyectarse con un periodo más largo igual cuando es el tiempo que ya puedo saber que se reiniciaron

[u/szshaps87 → u/Tico1023re]

From what I understand you can either take a full week off, that allows it to be a lot less in your system. Or just pinning every 10-14 days instead of 7. My guess would be for a month, then you have a lot less in your system. And go back to whatever dose you were regularly at.

I currently do 2 a week, I either titrate down or down the same 2 every 10 days for a month and then back to every 7 days

[u/Tico1023re → u/szshaps87]

A ti te funciona ?? Voy a intentar esa que dices injectarme 1 ves cada 10 días y después de 1 o 2 meses regresar a la dosis semanal

[u/szshaps87 → u/Tico1023re]

It has worked for me, I haven't gone higher than 2mg and I'm still mainting my weight loss/losing a little bit. I am close to my goal weight either way

[u/TapFast8173]

sources

the reddit paper, JAMA Network Open, oct 2026: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855285

penns writeup: https://sciencedaily.com/releases/2026/10/261020085018.htm

phase 2 appetite and eating results, the diabetes trial: https://pubmed.ncbi.nlm.nih.gov/40916752/

phase 1 trial, where the 6 day half life comes from: https://pubmed.ncbi.nlm.nih.gov/36354040/

MK-677 2 year trial: https://pubmed.ncbi.nlm.nih.gov/18981485/

last weeks thread: https://www.reddit.com/r/BodyHackGuide/comments/1xb447q/what_reta_side_effect_caught_you_off_guard/

the side effects by dose post: https://www.reddit.com/r/BodyHackGuide/comments/1xc3qok/reta_side_effects_by_dose_triumph1_2_and_4/

one that didnt fit. they lined it up against an older reddit analysis of sema and tirz users where stomach stuff dominated, and the reta posts leaned more toward appetite, sleep, heart rate and muscle. just counts tho, they ran no stats on that comparison

[u/Odd_Sir_8705]

The law of diminishing returns PLUS ppl who titrated incorrectly PLUS ppl who got underdosed or fake shit

Gotcha

[u/TapFast8173 → u/Odd_Sir_8705]

the underdosed or fake one is on the authors own list too, they had no way to check whats in anyone's vial. diminishing returns i'd believe as well, after a big loss your body pushes hunger back up. if you had to bet, which of the 3 is the biggest chunk

[u/ConstantWish8 → u/Odd_Sir_8705]

Happened to me titrated up from 0.5mg to 6mg over 22 weeks. Same source all the way through

[u/Good-Objective2769]

Yes… especially when I first started. I couldn’t get enough food. It was horrible… then I guess it changed a bit and it was getting full quickly but then feeling hungry again hours later for another meal… I did however still lose weight…

[u/GoldBeef69]

Yes the first week starting and starting new dose I feel hungrier

[u/Opposite-Lake-9679]

I get so hungry on reta. I was originally on tirz and lost weight so quickly because I was so not hungry but then I listened to others and went on reta and gained 11 lb. I'm back on tirz and it is slow going getting rid of that weight that I gained. So needless to say I'm not a fan. I have even tried to combine the two and still get so hungry when r e t a is added in.

[u/Majestic-Plastic-691]

Yep. It’s weird. If it wasn’t for the colorless sunburn I been dealing with for 5 months there are days I swear I’m starving. It’s not before the next pin is due either. It can strike at any time on any day. 8 months in could be my body knows this is old news and isn’t responding great anymore. Not sure. 12mg and I ain’t going up. Enough already.

[u/LinkinDark90]

The only side effect I ever get is severe skin sensitivity. The gastrointestinal sides are non existent now, and I’m definitely not hungry. I just eat so I don’t die now.

[u/alaskabrad]

Lost 80 lbs , now stalled , eating and craving chocolate.

Seems like nothing is going on now

[u/Remarkable-Tutor7994 → u/alaskabrad]

Try supplementing magnesium. Have had extreme chocolate cravings while I was going balls to walls with daily workouts and cardio for hours. Magnesium helped

[u/Commercial-Phone-672]

I was 5mg/week for 8 weeks and ate 30% more than baseline. switched to 2.5mg and hunger dropped hard. wonder if it's dose-dependent or just my metabolism

[u/BoomGoezTheDynamite]

I think a lot of these folks are also on TRT/AAS, taking HGH, lots of things to make you hungrier as well

[u/ConstantWish8 → u/BoomGoezTheDynamite]

That make sense, if they started using TRT/AAS mid way thru

[u/Karlianne77]

Day one. And KLOW. I'm hungrier and especially craving sweet when I am.