I keep circling back to the gap between the Phase 2 obesity readout and the company-reported Phase 3 numbers. Phase 2 had 24.2% mean weight reduction at 48 weeks under the efficacy estimand.
The Phase 3 press releases say up to 28.7% across four trials, but none are peer-reviewed yet. Is that jump mostly duration, different estimand, or baseline BMI? I'm also watching NCT05931367 because 445 enrolled with knee OA, but weight may be secondary there. What am I missing?
The 24.2% was efficacy estimand at 48 weeks, no? The 28.7% could be a different estimand or longer treatment. Not automatically comparable.
Source for the 28.7? Press release isn't peer-reviewed.
That's exactly my issue. A company slide and a peer-reviewed Phase 2 shouldn't be put side by side without the analysis set.
NCT05931367 is knee OA, 445 people. Weight might be a secondary endpoint there, so it won't settle the 24% vs 28% question.
Do we even know the Phase 3 durations? Four trials, up to 28.7%, but without weeks attached it's hard to compare to 48 weeks.
The estimand point matters more than people admit. Phase 2 efficacy estimand can exclude discontinuers, while Phase 3 might report treatment policy or on-treatment.
If the 28.7% comes from a completers analysis at a longer time point, it's not a clean jump. I'd rather see NCT05548231, NCT05931367, and the big 1946/2335 trials post results. The 32-person Chinese trial is too small to decide anything.
The 32-person trial is NCT05548231, right? I keep checking CTgov and it still says completed, no results posted. Frustrating.
Waist tape and weekly averages read a lot cleaner than the daily scale — that 24.2 vs 28.7 gap makes way more sense once you're looking at an actual curve instead of group means. Weeks 1–20 are dramatic, then weeks 36–48 flatten out to about 0.3 lb/week.
If the Phase 3 runs longer and keeps partial responders in, that alone could bridge a few points, no magic required.
I thought the trial jump was mostly baseline BMI until I tracked sleep for 8 weeks. On weeks I averaged under 6 hours, my loss was 0.2 lb/week; at 7.5+ hours it was 1.1 lb/week. Same food, same walking.
That won’t explain a 4.5-point trial gap by itself, but stress and sleep can absolutely make a 48-week readout look different from a 72-week one.
My weekends used to erase the whole week: Friday pizza plus Sunday brunch meant my Monday weigh-in was up 2–3 lbs, then I’d spend until Thursday getting back to Friday. I started pre-logging Saturday breakfast and doing a 20-minute walk after dinner, and my 12-week trend finally matched the 4-week trend.
It’s wild how much trial numbers depend on adherence and not just the molecule.
Honestly, I’d pump the brakes on comparing a Phase 2 efficacy estimand to Phase 3 press releases. Those PR numbers can be from completers, different groups, or longer treatment windows, so 28.7% isn’t automatically “better.” I’ve lot 18 lbs in 20 weeks, but my 4-week average bounced 2 lbs around ovulation and salt.
Until the full data are peer-reviewed, the jump is partly math and marketing.
My scale stalled week 30 but waist kept shrinking, so week 48 data can undersell longer trials.
Water weight masks the fist 3 weeks, then stalls hit week 6—weekly averages saved my sanity.
Under 6 hours sleep made my morning weigh-ins jump 2 lbs; stress eating, not the trial, moved my trend.
Dropout math can do a lot: if phase 3 keeps more completers, the efficacy estimand looks rosier. I track weekly averages and waist tape, and my loss looked 3% better at week 52 vs week 48 simply because I finally slept and walked daily.
So I’m less fussed about 24.2 vs 28.7 until we see dropout rates and how they handled missing data.
I’ve tracked waist at the navel every Sunday since week 1, and the scale-to-waist lag surprised me. Weeks 24-48 my weight loss slowed to maybe 0.3 lb/week, but my waist dropped 2.5 iches by week 52.
If Phase 3 ran longer than 48 weeks, that alone can explain a chunk of the 24.2 to 28.7 jump—the curve flattens, it doesn’t stop.
I actually disagree that the jump is mostly duration. I ran a 6-month experiment where I measured neck, chest, waist, hips every 2 weeks.
My scale was flat for 9 weeks after a vacation, but my chest and waist kept shrinking. That taught me trial weight-only percentages miss body comp.
But the flip side: baseline BMI. At my highest, 10 lbs was 3% of body weight; now 10 lbs is 6%.
If Phase 3 enrolled people with higher starting BMI, 28.7% could be same biology, different denominator.
Also, food tracking: I only lost consistently when I pre-logged breakfast and lunch, not dinner. Dinner was my chaos meal. So maybe trial sites with more structured food counseling get better numbers.
Adding a daily 25-minute walk after lnch changed my weekly trend more than anything else, but not the way I expected. The first two weeks my weight went up 1.2 lbs from soreness, then dropped 2.8 lbs over the next month.
I’d bet Phase 3 sites vary a lot in how much activity coaching they give, and that’s a hidden variable behind the higher numbers.
Honestly, a 4.5-point gap is smaller than my scale’s mood swings across one weekend.
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