Anyone else stuck on retatrutide's 28.7% vs 24.2% gap?

Baseline weight matters. Percent loss can look bigger in heavier cohorts.

The 'up to' wording is doing a lot of work. Is 28.7% from the primary endpoint or a subgroup? I have not seen that clarified.

Peer review will settle more than forum math.

I think the estimand debate is where this gets interesting. Efficacy estimand can look very different from treatment policy if dropout is uneven.

If the Phase 3 programs have more discontinuations, the company-reported 'up to' number might reflect a cleaner completers-ish picture. That does not make it fake, but it does mean we cannot line it up against 24.2% at 48 weeks without the protocol and missing-data plan.

The small completed trials n=32, n=445, n=46 may never publish weight outcomes either. That is the part I would want to see before trusting any cross-trial comparison.

The big CTgov enrollments, 1946 and 2335, could actually make an 'up to' result less comparable. Four trials pooled is not one trial.

Duration might be the simpler answer. 48 weeks in Phase 2; if the Phase 3 trials ran longer, more time could move the mean.

Fair, but Phase 2 used teh efficacy estimand too. If Phase 3 does the same, the gap is not just press-release spin.

The 28.7% is company-reported and not peer-reviewed, so comparing it straight to the 24.2% Phase 2 number is already shaky.

The estimand footnote is doing a lot of heavy lifting — efficacy estimand basically tosses out everyone who quit early, and in a 48-week obesity trial that's not a small group. My clinic's real-world numbers look way closer to the lower end, because people pause for surgery, travel, nausea.

I track weekly waist and a 7-day rolling scale average now; single weigh-ins lie to me constantly.

Duration mismatch is my bet. 48 weeks is right around where the curve tends to flatten hard — steady losses through month 6, then weeks 28-40 often look like bouncing inside a 3 lb window before anything moves again.

Another 20 weeks at that slower rate could easily add a few percent, so 24 vs 28 isn't necessarily a contradiction.

Honestly the 4.5% gap is smaller than my week-to-week water swings. I'd take either number.

Hot take: the 4.5 point gap is the least interesting number in those datasets. What actually predicts my results is whether I hit protein and steps on the bad weeks, not which trial arm looks better on a slide.

I'm 8 months in, down 41 lbs (212 to 171), waist 38 to just under 32, and every plateau I've broken came from boring stuff — 130g protein, 8k steps, lifting 3x a week, and actually sleeping 7 hours instead of scrolling until 1am. Weeks 20 through 36 I basically lost nothing and nearly quit.

If you'd shown me a 28.7% headline then I'd have felt like a failure at 19%. Now I just look at the 4-week trend line.

I keep coming back to baseline BMI. A cohort averaging around 41 sheds a bigger percentage for the same pounds than one sitting at 34, so percentage points aren't apples to apples across those five trials.

I track my own as % of starting weight and it gets flattering fast — 18 lbs off 232 reads way better than 18 off 300. Absolute kg would tell you more.

Press-release percentages don't meet a journal until someone's looking over their shoulder. I'll beleve 28.7 when it's in print.

Weekly average or you're just measuring your feelings. Weigh every morning, log it, compare Sunday to Sunday only, because a single day swings a few pounds on nothing — bad sleep, a salty dinner, whatever.

My own version of an "efficacy estimand" is the me that skips the two-week vacation where eating goes full chaos. Leave that stretch in and it drags every average down for a month.

Those n=46 and n=32 arms are the ones I'd toss first. In a 46-person group, two early dropouts or two super-responders move the mean a couple points by themselves. Not a knock on anything, just arithmetic. I'd rther see per-arm breakdowns from the 1946-person trial than a headline top-line number.

Baseline BMI is the sneaky one for me—if the Phase 3 pool averaged a higher starting weight, 4.5 points can be partly population math, not a better drug. I’m 5-6 and at 240 vs 190 the same 10% looks totally different on my frame.

Also, dropouts: if 15% quit early and aren’t counted the same way, the mean gets rosier. I’d want the denominator before getting excited.

Chasing trial percentages stops being the point once the week 52 numbers come in. Real-world version people report: scale down 17%, waist down 7 inches, shirts going L to M.

The weird part is usually a 9-week stretch around month 5 where the scale barely moves while the belt keeps tightening. And when a Phase 3 reads 28.7%, if it came from a longer run or a group that stayed on treatment, that 4.5-point gap is probably time and adherence more than magic.

Then there's the version that goes the other way — 22% down but the waist barely changed, which lines up with muscle coming off, so the tape measure tells on that one. The headline number ends up mattering a lot less than the waist measurement and how the training log looks.

Honestly the 28.7% won’t mean much if your own week 24 is flat and your jeans fit the same.