48-week 24.2% vs Phase 3 28.7% — what gives?

I keep a sheet too. The 1,946 and 2,335 trials are where I’d look for 28.7% context.

Population matters. The nkee OA n=445 cohort may have lower activity, so the curve could look different.

Glucagon receptor agonism is the wild card. More energy expenditure sounds good until glucose drifts.

The 24.2 vs 28.7 gap could just be estimand. Efficacy estimand isn’t company Phase 3 topline.

I’d be cautious comparing 24.2% to 28.7% directly. The Phase 2 number was at 48 weeks, while company Phase 3 reports may use different analysis sets, baseline BMIs, and discontinuation handling.

Add the CTgov enrollment spread—32, 445, 46, 1,946, 2,335—and these cohorts are not interchangeable. Without peer review, I’d compare within trial only, not headlines. I’m not saying the higher number is hype; just that estimand and population matter.

What would convince me is a full 48-week curve by baseline BMI and glycemic status, plus discontinuation rates. That would separate a design artifact from a genuine efficacy difference.

The n=32 Chinese trial tells us almost nothing.

Agreed, don’t mix cohorts. Want glucagon markers, not just weight.

I've been nerding out on this too, and the estimand thing flipped it for me. That 24.2% was an efficacy estimand at 48 weeks, which basically answers "what happens if everyone stays on and takes it as assigned" — phase 3 press releases tend to lead with the on-treatment or treatment-policy number, and those can diverge 3-5 points purely from how dropouts get counted.

The enrollments don't look weird to me either: n=32 reads like a titration sub-cohort, 46 and 445 look like PK or dose-finding studies, and the 1,946/2,335 are outcomes trials where 48-week weight isn't even the primary endpoint. Baseline BMI and country mix matter a lot.

I've logged weekly since week 4 and my 4-week rolling average sat flat for six straight weeks around week 30, then dropped 3.1 lbs in ten days. Short windows lie constantly.

Adding a boring variable nobody talks about: sleep. I ran 5-6 hours a night for two weeks during a work crunch and my weekly loss went from 1.4 lbs to basically 0.2, appetite came roaring back, scale didn't move for nine days. Got back to 7.5 hours and it unstuck within a week.

If phase 3 sites have tighter follow-up and support than a small phase 2 cohort, that alone could be a pint or two of the gap.

Contrarian take: I'd trust the 24.2% over the 28.7% until there's body comp data. I'm at week 40, down 21% by scale, but my waist is down 7.5 inches and a scan around week 32 showed a real lean-tissue chunk in there that I'm not thrilled about.

When my weekly loss rate got aggressive, the lean share got worse, not better. A faster-losing phase 3 population could absolutely post a bigger headline number that's partly water and muscle.

Also "up to 28.7%" is the best arm of the best trial, not the average, and my own best 12-week stretch looked way better than my actual 40-week total. Has anyone seen waist-to-height data from these arms?

I'll push back on the enrollment thing — that spread isn't odd, it's just how these programs get built. A 46-person trial is almost certainly a PK or regional bridging study, 445 is dose-finding, and the two ~2,000 arms are outcomes trials where weight is a secondary readout.

Different baseline BMIs, different countries, different food environments. Where I do think something's off is timeline. I'm at week 52 and my last 10 weeks have been pure maintenance, 0.4 lbs total, so a 48-week number and a 68-week number aren't comparable at all.

If phase 3 is quoting a later timepoint than 48 weeks, that alone could be most of the 4.5-point gap.

I weigh every morning but I only look at the 7-day average. Daily noise for me has swung as much as 3.1 lbs. Week 34 was flat to the ounce versus week 28, then I dropped 2.4 lbs over nine days doing nothing differently.

If the Phase 2 number came off single-visit weights and the Phase 3 readouts smoothed that out, a percent or two of your gap is just arithmetic, not biology.

The tape measure at my navel beat the scale for two straight months. Weeks 20 through 27 my weight sat inside a 1.2 lb band, but my waist went 41.5 down to 39.75 and I dropped a belt notch.

If one trial protocol tracked waist and another only tracked pounds, the two numbers aren't describing the same thing. Are you logging anything besides the scale?

Restaurant weekends are my entire swing. Two dinners out with soy sauce and I'm up 4.2 lbs Monday, right back down by Thursday. That's roughly 2% of my body weight moving on salt and nothing else.

If trial visits land on a fixed schedule, one cohort getting weighed after a holiday stretch versus a normal week could eat a real chunk of that gap you're chasing.

Total weeks actually on treatment is the column I'd want next to those percentages, not just 48 versus whatever the Phase 3 duration was. I stalled from week 29 to week 41, twelve weeks and 1.1 lbs total, then dropped 6.3 lbs over the next ten weeks with zero habit changes. Bodies stair-step, they don't slide.

If the Phase 3 figure is a readout point where more people have already banked their own week 60, part of the higher number is just longer runway.

The other part is likely who got enrolled, since a wider pool with higher starting BMIs makes percentage loss look better because there's simply more to lose. That's not extra effect.

What I'd trust is pounds lost compared at the same week count per person.

Those 32- and 46-person enrollments are the tell for me. In a 32-person trial, one person dropping 40 lbs can swing the mean by over a point, so a flashy 28% can easily be a couple of super-responders plus small-sample noise.

The 1,946 and 2,335 trials are the ones I’d actually weight, and they’re closer to the Phase 2 24.2%.

A 32-person arm is basically a group cat wearing lab coats.

My 4-week rolling average hides the daily chaos way better than any single morning number.

Sleep under 6 hours for three nights and my weekly loss basically flatlines.