24.2% Phase 2 vs 28.7% Phase 3: What Explains the Gap?

The 24.2% was efficacy estimand, not treatment policy. That alone can explain a few points depending on discontinuations.

Duration's the other one people gloss over. 48 weeks in Phase 2 vs the longer Phase 3 windows — and in both cases weight loss probably hadn't plateaued yet. Worth keeping in mind before comparing the numbers side by side.

Everyone compares company PR to peer-reviewed Phase 2 like it is apples to apples. It is not. Wait for full Phase 3 tables.

I printed the CTgov pages and taped them above my desk. The estimand row alone made me pause. Treatment policy versus efficacy can look like two different studies, even when the visits line up.

Short version: not head-to-head. I keep saying this. Different baseline BMI, different weeks, different analysis sets. The gap is a pile of small things, not one villain.

What jumped out at me isn't duration, it's how many people were still in the study at the readout.

The earlier one had a chunk of early discontinuations, and if those folks get excluded from the efficacy estimand, the group left over is basically the people who tolerate it best — that's a survivorship number, not a population number. Phase 3 kept more people on board, so its mean drags less.

Check the completion rates side by side.

Baseline weight does a lot of quiet work here. Losing 40 lbs from 220 is 18%; losing 55 from 265 is 21% — same drug, same effort, different denominator.

If Phase 3 enrolled heavier, some of that 4.5-point gap is arithmetic, not biology. I'd want mean starting BMI for both before crediting anything else, and honestly the median might tell you more than the mean.

I keep circling back to NCT0554823 and whether anyone split the results by region. East Asian cohorts often start at lower BMI but carry more visceral fat at that same BMI, so a percent-of-bodyweight endpoint can undersell what's happening at the waist. Did that trial report waist circumference, or just scale weight?

If it's scae only, then 24.2 versus 28.7 is two different measurements pretending to be one.

Personal thing that made me stop trusting the duration argument: the body-comp numbers in my tracker — down about 9% over the first 16 weeks, flat from roughly week 18 to 30, then another 6% between months 8 and 11. Best stretch was the back half, and nothing changed except finally tracking protein (aiming 130g) and walking 8k steps with a podcast.

The intervention didn’t get stronger; the habits just showed up late.

So if Phase 3 ran longer, the extra time may not be harvesting more drug effect, it may be giving behavior change room to compound. Still, does Phase 3 publish a week-48 snapshot of that same cohort? Hold duration constant and whatever’s left is population.

My week 12 plateau hit exactly when I changed my Saturday routine, so I stopped trusting single weigh-ins and switched to 7-day medians. In my logs, a salty Sunday can swing me 2.3 lbs by Monday and 0.8 by Wednesday.

If a trial endpoint is one visit, that noise could move a group mean by a point or two, especially with small arms. I’m not trying to explain the whole 4.5-point gap, but endpoint timing and who shows up that day might do quiet work.

Weird part: during a 3-week scale stall my waist dropped 1.5 inches, so the tape kept me sane. Has anyone else compared their weekly average to the clinic weigh-in and seen a different story?

Sleep was my hidden variable. I traced 6.5 vs 7.5 hours for 8 weeks; under 6.5 I averaged 0.2 lb/week lost, at 7+ I averaged 1.1 lb/week, same meals and walks.

The surprise was that a bedtime alarm did more than adding a 45-minute gym session. I know it’s n=1, but if one arm sleeps worse, the percentage gap gets weird fast.

My jeans size is the only metric that hasn’t lied to me since week 6.

Weekends are my personal Phase 3: same plan, two dinners out, completely different graph.

The gap I keep landing on isn't trial length, it's how adherence gets counted. My own 48-week log looked like 24% down by week 24, then only added about 4% by week 48 because I quit tracking dinners.

If Phase 3 had more visits or completers, that alone could add a few points. Did the CTgov entries list discontinuation rates by arm?

Baseline BMI is the sneaky one. I started at 41 BMI and dropped 10% in 12 weeks; a friend started at 31 and lost 6% in the same window.

Higher starting weight can inflate early percentages without meaning the trial was longer or the population was that different. Do the CTgov entries show mean baseline BMI? That would move my needle more than country.

My scale swings 4 lbs on pizza night, so I trut monthly averages.

I’d bet on the estimand switch, not the Chinese cohort.

Week 40, down three belt notches, scale says 11 pounds. Phase percentages never fit one actual body anyway.

Sleep is my hidden variable, and I got it backwards for months. Same food, same walking, but a 5-hour night versus 8 hours swings my morning number 2-3 pounds and my next-day hunger is a different animal.

Weeks 1-20 I slept well and dropped steadily; weeks 21-30 both kids had croup and everything flattened. I blamed my food. It was the sleep. A tidy trial week isn't my February.