24.2% at 48 weeks vs 28.7% in Phase 3 - what gives?

We don't have lean mass numbers in the trial facts we have, so I wouldn't guess. But the glucagon piece is why retatrutide gets attention beyond GLP-1/GIP. That doesn't automatically mean better body composition.

The CTgov entries for NCT05931367 and NCT06039826 don't give headline results, so we're stuck waiting on peer review. Also, NCT05548231 only enrolled 32 people, which is tiny for any body-comp claim.

Dose-response matters, but the glucagon piece is what I'm curious about. Triple agonist, so GLP-1/GIP/glucagon. I care less about scale weight if lean mass is tanking.

Not sure duration alone does it. If 28.7% is a top dose arm and 24.2% is a trial mean, that's apples to oranges.

Duration is my guess. Phase 2 looked at 48 weeks. Phase 3 may run longer. Knee OA and postmenopausal groups aren't the same as general obesity either.

Maybe, but completed trials are way bigger - 1946 and 2335 in two. Bigger n doesn't magically push mean weight loss up unless duration or dose differs.

The 28.7% is company-reported and not peer-reviewed, so I'd treat it as a headline, not like-for-like. The 24.2% was efficacy estimand. Different estimands alone explain a chunk.

Up to is doing a lot of work there; 28.7 sounds like a best-case arm, not the average.

Timeline mismatch is the first thing I’d check. Phase 2 says 48 weeks; the Phase 3 figures may be from different readout weeks, so 28.7 could be a later snapshot.

I’ve tracked my own weekly averages for 9 months and the 6-9 month slope looked nothing like months 1-3. What week were those Phase 3 percentages measured at?

Baseline size changes what a percentage means. I started at 246 lbs; 10% was 24.6 lbs and my knees felt it fast. A 180-lb person losing 10% is 18 lbs.

Those Phase 3 trials had very specific groups—knee OA, postmenopausal, small n—so the 28.7 could reflect who enrolled, not a stronger effect. Do you know baseline BMI for each?

Headline % is almost never the lived weekly experience.

Daily weigh-ins, but only Sunday averages get compared. Waist at the navel. Sleep and step count in the same note. Everything else is noise.

First three weeks: 6.8 lbs, mostly water. Weeks 12-20: 0.7 lbs/week, and the whole reason was weekend takeout and bad sleep, nothing mysterious. Weeks

I weigh every morning but only count Sunday after bathroom, naked, same scale.

Funny thing: weeks my scale flatlined, my waist still dropped half an inch, so a 24% vs 28% headline would feel totally different depending on whether they measured scale or tape. Did the postmenopausal or knee OA groups track waist, or just pounds?

My sleep tracker averaged 5h42m for week 20 and my scale sat at the same tenth for 11 days. Then I got two 8-hour nights on a camping trip and dropped 2.3 lbs without changing my food.

That kind of swing makes me wonder if Phase 3 sites even log sleep or stress, because 4.5 percentage points could be a lot of bad sleep.

Water weight can fake a 3-lb whoosh overnight; percentages don't care, but my pants definitely do.

Small n is my sticking point: 46 postmenopausal and 32 participants are tiny. If 6 people drop out, the mean can swing several points from one big responder.

I’d rather see the completers’ curve and dropout reasons than a topline 28.7%. In my own log, one 5-lb water dump after a salty weekend made a 12-week average look way better than it was.

Wait, are the Phase 3 numbers at 68 weeks? If so you're comparing a 48-week slice to a longer run.

My husband lost 9 lb just from cutting beer; trials with diet support aren't pure drug effect.

I ran a 12-week office weight pol and the folks who dropped out were exactly the ones who'd have blown up the average. If Phase 3 reports completers or a different estimand, 28.7 vs 24.2 is noise until the missing-data rules match. Also check if baseline BMI was higher; heavier start often means bigger drop.

My waist tape moved 2 inches before the scale caught up, so I trust trends over exact numbers.

46 postmenopausal participants and 32 in that third one, those arms are way too small to average in with 445.