Retatrutide Phase 2: 8mg vs 12mg week 36 plateau

I noticed that shape too. The 8mg and 12mg error bars overlap by week 48 in the appendix, so the plateau might be noise.

Overlap isn't proof of noise. 12mg is still lower at every visit after week 20, which looks like a dose signal.

Probably GI dropout. If 12mg is what's holding onto the people who can tolerate it, a completers analysis ends up looking better than ITT.

Does the supplement list observed cases or just LOCF? I only have the main PDF.

It has both. The week 36 N drops more in 12mg than 8mg, which matters.

If side effects drive dropout, wouldn't that bias the 12mg completer curve downward? More tolerant people stay, so the drug looks better.

Not necessarily. People who lose less may also quit, so completer curves can exaggerate either direction.

Can we stop pretending 8 vs 12 is a huge split? 1.4 percentage points at 48 weeks is marginal.

Depends on baseline weight. 1.4% of 120kg is 1.7kg, not nothing, but not a clean separation either.

I asked a stats friend about this. She said the trial wasn't powered for pairwise 8 vs 12 at 48 weeks; it was powered for overall dose-response. So the visual gap can be real and still not statistically robust.

The better question is whether the exposure-response curve is monotonic across the whole trial, not whether two arms split at one visit. If you can find the PK/PD supplement, that would tell us more than squinting at arm-level means.

Also, the 12mg arm had more dropouts, so any completer-based plot is going to be selected. I would not read week 48 as a clean 12mg win without the per-visit Ns and a sensitivity analysis.

Same. ClinicalTrials.gov results tab sometimes has cleaner per-visit Ns.

Per-visit Ns are in the appendix, but they're buried under a footnote in table S4 and I gave up scrolling.

My plateau at month 8 broke when I started weighing food again, not when anything changed on my end dose-wise. Turns out my "small" portions had crept up maybe 200 calories a day over three months. So whn I see a curve go flat I always wonder how much is pharmacology and how much is everyone getting comfortable.

My scale sat flat for nine weeks while my waist wnt from 36 to 33. Means don't show that.

The thing that bugs me about reading it off the plotted means is that the higher arm keeps bending down partly because the people who couldn't hack it already left. If tolerability dropouts cluster in weeks 12 to 28, then by week 36 you're averaging a tougher, more tolerant subset, while the lower arm still carries more of its original mix in the denominator.

I'd want per-visit Ns printed next to every mean before calling it dose-response, because a 10% shift in who's still showing up can move a mean a point or two by itself. Mixed models only bail you out if the missingness is random, and with stomach stuff it basically never is.

My worst stall started the week my sleep fell to about 5.5 hours a night — six weeks bouncing between 187 and 188.4 on identical food and the same evening walks. Went back to 7.5+ hours with a boring consistent bedtime, changed nothing else, dropped 4.6 lbs over the next three weeks.

So whenever I see a kink at a specific week on a curve, I wonder how many people in that arm were sleeping like garbage by then.

Friday through Sunday I was running roughly 2,000 extra calories a week — not binges, just two restaurant dinners, a couple of IPAs, and the usual Saturday grazing. Average that over seven days and it's about 300 a day, which was the exact size of my deficit.

Weekdays looked spotless, so for two months I blamed my metabolism.

Kept weekends the same and made weekdays slightly lighter instead, lost 2.8 lbs in three weeks.

@fit_jose said:

Weekdays looked spotless, so for two months I blamed my metabolism.

I'll push back a bit: a 1.4 point gap between the two top arms, with CIs that wide, isn't something I'd call a real divergence, and one kink in a plotted mean is more likely noise and visit timing than biology. My own scale jumped 3.1 lbs in four days after a salty dinner and was back down by Tuesday.

Curves that smooth are hiding that much wobble per person.

I added 40-minute walks after dinner, five nights a week, around month five, and the scale basically yawned for six weeks — 201 to 200.2 while I was doing more than I had in a year. Then over the next five weeks it dropped 6.4 lbs and I changed nothing in that stretch.

My theory is the walking was real but masked by water, plus my appetite came back harder on walk days so I was eating an extra 150-200 calories without noticing. The unexpected part: the week I went on vacation and quit the walks entirely, the scale didn't move at all, which told me my earlier whoosh wasn't the walking finally kicking in, it was just timing.

Now I judge by whether my usual jeans need a belt, not by any single week on the graph.