24.2% vs 28.7%: how are people reading Retatrutide Phase 3?

2026-09-14 10620 views 58 posts

I keep going back to the Phase 2 result: 24.2% mean weight reduction at 48 weeks under the efficacy estimand. Then company-reported Phase 3 says up to 28.7%, not peer-reviewed yet. Those aren’t apples to apples, right?

I’ve also been staring at CTgov: NCT05882045 enrolled 1946, NCT05929066 enrolled 2335, knee OA 445, postmenopausal 46, Chinese cohort 32. A few are completed but no headline results in the raw record. What’s the useful way to compare these without overreading press releases?

I’m less interested in hype than figuring out what the actual endpoint definitions and populations are doing.

Efficacy estimand is the key. It’s not the same as a simple average of everyone who enrolled.

Agreed, but the 28.7% was company-reported arcoss four Phase 3 trials, so it’s likely a high dose or completer-heavy slice. Not comparable.

I’ve been in a similar rabbit hole. The CTgov records for the small completed trials you listed are frustrating because enrollment is there but no outcome tables.

That doesn’t mean nothing happened; it often just means results aren’t posted yet. The 24.2% Phase 2 figure at 48 weeks is the cleanest number we have because it’s tied to a defined estimand. The 28.7% is company-selected language from four trials. I’d wait for peer review before treating them as one curve.

What would convince me is seeing the actual dose groups, not just the top-line up-to number.

Same. Up to means someone in some arm hit it. Doesn’t tell us the distribution.

Endpoint definitions are where the bodies are buried.

Population might matter more than endpoint definitions here. The 445 knee OA trial has a different baseline; I wouldn’t expect identical weight loss.

Week 14 here and my scale did the opposite of the headlines: down 1.1 lb/week for the first 10 weeks, then flat for 5 straight weeks while my waist tape dropped 2 inches. That's why I don't treat either percentage as a personal forecast.

A trial mean is built from people who stayed on it the whole time; my body doesn't read press releases. 24.2 vs 28.7 is a population stat, not a promise to me.

48 weeks is where the framing deserves some pushback: 24.2% is an efficacy estimand, which basically means "if participants stay on it as assigned" — the trial's version of a perfect patient. So 28.7% in phase 3 isn't shocking, it's the same story with a bigger sample and a different analysis plan.

The part people forget is weekends. Friday takeout and two glasses of wine, Sunday the scale is up 3.4 lb, gone by Wednesday.

Ten weeks of that and the real trend was 0.7 lb/week down, not the 2 lb/week those Monday weigh-ins implied. Which is why the advice that keeps circulating is: log daily and only read the seven-day average.

The knee OA one is a different animal — 445 people, and the endpoints there are pain and function scores, so any weight change is likely secondary and not comparable to the obesity trials at all.

What I want to know is whether the 1946-person and 2335-person studies used the same estimand; if they didn't, stacking their headlines against phase 2 is just noise. Conference abstract or journal, do you think?

Month three was my mess: I added 45 minutes of walking five days a week and started sleeping 7.5 hours instead of 5.5, felt amazing, and the scale went UP 2.1 lb and sat there for twelve days. I nearly quit tracking entirely.

Then it dropped 6.4 lb in nine days and my jeans went from a 36 to a 34. Water and inflammation noise, not fat.

Lesson I keep relearning: 12 days is nothing on a 48-week timeline, so a phse 3 average is even less useful for any one person. I only trust the monthly waist tape now, same spot, first thing, empty.

@hollySteady38 said:

12 days is nothing on a 48-week timeline

The number that actually makes me squint is dropout and missing-data handling, not the 4.5-point gap. If the Phase 3 headline leans on people who stayed the course, 28.7% is the best-case version. I track a 7-day average now because one salty weekend can swing me 2.8 lb, so a single timepoint tells me almost nothing.

Peer review or it’s just a highlight reel. I’ve been burned by pretty graphs before.

I quit chasing the trial percentages and bought a cheap tailor’s tape. My scale has been flat for 19 days, but my waist is down 1.25 inches snce week 10, and my jeans finally don’t leave red marks. That’s the weird part—non-scale wins sometimes move first while the headline number stalls.

The CTgov enrollment sizes tell you the trials are huge, but my personal n=1 says stress and sleep muddy everything. A rough work week with 5.5 hours sleep and two takeout dinners had me up 3.1 lb by Friday, gone by Tuesday. So when I see 24 vs 28, I think: whose week? whose water? whose life?

I quit weighing daily around week 6 because the water swings were louder than the trend. Switched to Sunday morning waist tape and one pair of jeans. Lost 2.5 inches before the scale moved 4 lb. So when I see 24 vs 28, I mostly wonder whose mornings those averages came from.

Mine would look totally different on a Monday after salt and a bad night’s sleep.

Honestly, 28.7% doesn’t mean much to me until dropout rates show up; that’s the number that says who could actually stay on it.

Weekends are the real stress test for anyone tracking food and sleep: five decent days, two feral ones, and Monday's scale acts like we just met.

Worth remembering what the "up to 28.7%" figure actually describes. The curve most people end up comparing themselves to looks more like: 8 lb down by week 8, 14 by week 20, then flat for six weeks even with lifting and 10k steps most days.

The next drop came after a month of actually sleeping 7.5 hours, not after chasing the number harder. So "up to 28.7%" reads as the best-case timeline, not what happens at the 48-week mark for most humans.