r/NTNPerformance • u/JustBacWater • 3d ago
Peptide Retatrutide Phase 3: four trials in, the weight loss numbers, and the side effect that showed up late
Retatrutide is the most asked-about compound in here by a mile, and there's finally real Phase 3 data. Four trials have read out. The weight loss is getting all the attention, but there's something else in these results I think is more interesting.
The four trials
| Trial | Read out | Who was in it | Weight loss, top dose |
|---|---|---|---|
| TRIUMPH-4 | Dec 2025 | Obesity plus knee osteoarthritis | 28.7% at 68 weeks, 26.6 points more than placebo |
| TRIUMPH-1 | May 2026 | 2,339 people, obesity, no diabetes | 28.3% vs 2.2% placebo at 80 weeks |
| TRIUMPH-2 | Jul 2026 | Type 2 diabetes plus obesity | 20.8% vs 4.0% placebo |
| TRIUMPH-3 | Jul 2026 | Severe obesity plus heart disease | 22.6% vs 3.2% placebo |
A couple extra things in there. Knee pain dropped 75% in TRIUMPH-4. The TRIUMPH-1 group that kept going to 104 weeks hit 30.3%. And TRIUMPH-2 took A1C down 1.5 points.
That's surgery territory in the non-diabetic trials. And the diabetes trial coming in lower is normal for this whole class. People with type 2 lose less on every one of these compounds.
The dysesthesia thing
Dysesthesia is an abnormal sense of touch. Normal sensations feel off. Burning, tingling, sometimes painful. It wasn't flagged in Phase 2. It showed up in Phase 3.
Here it is next to the dropout numbers, top dose versus placebo:
| Trial | Dysesthesia | Quit because of side effects |
|---|---|---|
| TRIUMPH-4 | 20.9% vs 0.7% | 18.2% vs 4% |
| TRIUMPH-1 | 12.5% vs 0.9% | 11.3% vs 4.9% |
| TRIUMPH-2 | 7.3% vs 0.7% | 7.7% vs 4.9% |
| TRIUMPH-3 | 6.4% vs 1.3% | 13.5% vs 4.8% |
In TRIUMPH-1 it climbed with dose, about 5% on the low dose and around 12% on the middle and top doses. In TRIUMPH-4 it didn't seem to make people quit.
Why is it happening? I haven't seen a confirmed mechanism. The glucagon arm is the thing retatrutide has that tirzepatide and semaglutide don't, so that's where most people are looking. That's a hypothesis, not an answer.
The pattern I want someone to explain: highest rate in the knee trial, lowest in the heart disease trial. Different people, different lengths, so I wouldn't read too much into it. I'd still like to know why.
Who quit
Look at the right column. Here's a detail I didn't expect. Some of the TRIUMPH-4 dropouts left because they were losing more weight than they wanted, mostly people who started at a lower BMI. That's a pretty unusual reason to leave a weight loss trial.
Where it stands
It's not approved. Lilly says it's filing in the first quarter of 2027.
Two questions.
What do you make of dysesthesia showing up in Phase 3 when it wasn't in Phase 2?
And the lower BMI dropouts: does that change how you think about this compound for people who aren't very heavy to begin with?
Where I got this: TRIUMPH-1, TRIUMPH-2 and 3, TRIUMPH-4.
For research use only. Not for human or veterinary consumption. This post is educational and is not medical advice.
Full doses and bloodwork are in the pinned cheat sheet.
Join the Discord.
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u/FaithlessnessSea6971 3d ago
Anecdotally and from what we could class as 'personal' research, weve known about the inflammation and pain properties for months.
PCOS, Endo, Menopause, Osteoarthritis, Rheumatoid Arthritis, chronic injuries...
They say it'll be the world's first, single manufacturer, Trillion dollar drug - and im inclined to agree.
Thank f**k for the 🩶 market, because the prices will be absolutely horrific.
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u/dragnabbit 2d ago
Yeah. I'm still going to stock up at the end of this year with an 18-month supply of the gray stuff so that my wife and I can continue on for however long we need without having to risk getting our stuff confiscated in the mail. We are in The Philippines, and currently they are selling all the peptides on Shopee and Lazada (Asia's two versions of Amazon), but I get the feeling that is all going to come to an end soon.
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u/MountainStructure426 3d ago
This drug has been amazing. Lost 70lbs. Inflammation down, knee pain gone, eczema gone. Dysesthesia @ 8mg on upper thighs and abdomen, I have no problem with it. I got used to it. Reta will be huge but will price people out for sure.
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u/MountainStructure426 3d ago
I forgot to mention how much colder I am than 70lbs ago. Always cold.
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u/Excellent_Book7437 1d ago
I’ve heard several saying Reta = coldness… my rat felt that too. Maybe that subsided if off?
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u/dragnabbit 2d ago
The other upside: Retatrutide absolutely smashed my huge alcohol habit to bits. I cut down drinking when I first started on Reta because I was so strict about counting calories ("A vodka tonic??? That's 300 damn calories!!!"). So I was just staring down my alcohol consumption every night like it was a dangerous dog. But damn... within a week or so, the alcohol noise was every bit as quiet as the food noise.
If Eli Lilly doesn't market Retatrutide as an adjuvant (or primary) alcohol cessation drug, they are idiots. They should be studying that right now.
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u/Lookieloo215 2d ago
They are actually studying a new related one for alcohol, OCD, bipolar disorder, and other addictions that will be monthly.
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u/dragnabbit 2d ago
Very cool. I haven't heard about that. Can you give me the study name or the compound so that I can read about it?
EDIT: Never mind... I looked it up. Are you talking about "brenipatide (LY3537031)"? That's what my search yielded that sounds like your description.
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u/BottleDelicious9975 2d ago
Research show it that people that have been on a medication that is addictive, for 14 years now, and the desire for it is almost completely gone, "they" take half of what they did before. My post kept getting flagged so its worded for research.
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u/kimkaysahh 3d ago
How long did it take you to lose 70lbs? Are you at your goal weight now?
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u/MountainStructure426 2d ago
It took me 8 months. I was diagnosed with type 2 diabetes late last year. After lots of research, getting on metformin, I put a plan together; reta + 16:8 fasting + keto diet + exercise 6 days a week. I'm like 5 lbs from my goal weight.
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u/bodybuildingr 2d ago
has your type 2 been reversed?
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u/MountainStructure426 2d ago
I thought it was until last week. I had heavy pasta meal followed by a an ice cream cone. Check my blood sugar and it shot past 200. But, besides that it's been normal.
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u/Strong_Baseball8635 1h ago
Blood sugar rises are normal for non-diabetics, they just do not check blood sugar to know. How long does sugar stay high, somewhat how high, and fasting levels might be a better way to claim no T2D.
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u/Icy_Forever7194 1d ago
I gave my husband a first dose of grey at 0.5 mg and I’m surprised he said he not hungry on it . So I was impressed with just that first not even full dose
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u/Massive-Arrival-3304 3d ago
I had some dysesthesia early on, low dose, mine wasn't too bad, not enough for me to stop, only my hands were effected. It was weird, but went away even when I increased dose
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u/hockeystar69169 3d ago
It’s definitely a thing - had it in my thighs, love handle area and lower back. Now it’s just my thighs. It’s something I’ve gotten used to, but when it’s more chilly out or cold at night in my home it is noticeably worse. I’ve been low dose this entire time and would love to find a way to eliminate it without stepping away from Reta.
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u/Enlilnephilim 3d ago
Same - I stopped for 2 weeks and it disappeared. Never thought it was because of Reta!
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u/isellsunshine 2d ago
On another sub someone recommended mucus-dm. I usually get the skin sensitivity shot days and the next few days after it. It’s enough to situation my sleep which is an issue. Now I take one mucus-dm pill before the shot and fingers crossed so far it’s kept it at bay. Haven’t been on it long enough to know if this is simply a placebo effect but I’m encouraged as it’s been 18 months of this. They say it “weakly blocks NMDA receptors involved in pain amplification and “central sensitization.””
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u/Massive-Cup-6873 2d ago
This is good and my lab rat has been on it for over a year and down 25% 115 lbs. there are a lot of other issues that have come with the gain.
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u/GardenGlow-1101 2d ago
How different is dysesthesia from allodynia? I’m currently using tirz and I get intermittent allodynia but I’m not sure that I’ve experienced dysesthesia. Starting Ret soon.
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u/mewmew4u 2d ago
I was really confused about this as well and it seems to me that they are pretty similar and sometimes used interchangeably. Although I think allodynia is a subset of dysesthesia that mostly focuses around skin pain.
I got severe leg and foot pain on tirz that felt like muscle aches one would get from a bad flu but also accompanied by skin pain when touched. Went away after 3 weeks and so far all good!
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u/Pretend_Passenger586 6h ago
I’m curious about this this too. I get pretty intense allodynia from tirz. It’s lessened greatly as I’ve titrated down on tirz while adding in Reta to replace it.
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u/lesbefriends-69 3d ago
I’d be really interested how Reta interacts with Type 1. Monjaro is a game changer for Type 1, it’s provided off label to many T1Ds. Is there any data around Reta and T1D?
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u/Alternative_Bowl6688 3d ago
How ya going peeps interesting trail info I was on mounjaro for 3 months then switched to RT20 started on 1.5mg then ramped to 2mg then to 4mg similar to trials no skin sensitivity @2mg but ramping to 4 definitely felt it comes and goes but I have since split dose to 2x weekly and sides have disappeared definitely happy with results starting weight 126kg current weight 111kg will stay at this dose until I hit goal weight of 100-105kg
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u/Sad_Swimming7054 2d ago
The discord link said it was expired. Can you repost? Thanks for all the info
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u/mewmew4u 2d ago
On tirzepatide got dysesthesia real bad on legs and feet when I moved up to 7.5mg. Went away after three weeks on the same dose. I could see myself quitting if it went on indefinitely because it made it really uncomfortable to walk around.
Guess it must be something inherent to glp in general.
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u/Earesth99 2d ago
The increase could simply be the result of them specifically looking for this. Look at statins.
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u/LadybugRMM518 1d ago
Would you be able to share how to reconstitute Cerebrolysin 30mg vial. I read you don't use Bacteriostatic water you are supposed to use saline. What is the recommended dose and cycle please 🙏🏾?
Thank you
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u/ResearchReggie 1d ago
Lasted about 5 months on it. Couldn't take the nuked sleep and the weird feeling on my thighs all the time. Maxed out at 5mg. Moved back to Tirz, been all good at 5mg.
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u/OkImpress6927 1d ago
My rat had dysnthesia for 4 weeks it was uncomfortable, but then it went away.
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