Phase 3 28.7% vs Phase 2 24.2%: what am I missing?

Peer review matters. Company 28.7% could shrink later.

The 24.2% was efficacy etsimand, not a completer average. That can explain part of the gap.

A1c 5.8 to 5.4 is solid. How long?

Your fasting glucose drop is almost 16 points. Yeah, glucose often moves before weight early on.

I've been digging into the CTgov entries. NCT05548231 enrolled 32, NCT06039826 46, and NCT05931367 was the knee OA study at 445. The two bigger completed studies are NCT05882045 at 1,946 and NCT05929066 at 2,335. That is why I would not compare your single log to 28.7% at all. The Phase 2 24.2% at 48 weeks is already a mean, and the Phase 3 press releases are not peer-reviewed. Your A1c change is interesting though; glucose shifts can lag or lead weight change depending on the person.

I'd take 18% at 48 weeks. Small trials aren't powered for 24 vs 28.

But if the big Phase 3 enrolled different BMI ranges, the percentage gap might be baseline effect.

Exactly. The knee OA arm was 445 people, so not tiny, just not the main obesity cohort.

I plugged the percentages into my own starting weight instead of comparing the percentages head-on: at 231 lbs, 24.2% would be 175 and 28.7% would be 165. So the phase 3 'step up' is about 10 lbs for someone my size, not a whole different universe. My 48-week drop was 18.2%, and it was lumpy as hell: stuck at 201 for almost five weeks, then 189 after a vacation where I walked 12k steps a day. Trial means hide that; they also depend on baseline BMI, how dropouts are counted, and whether the phase 2 population had more people with T2D or different adherence. The 1,946 and 2,335 trials are big enough to matter, but still not peer-reviewed. I'd read 28.7% as maybe real but probably a different population plus support, not a magic new level. What was baseline BMI in the phase 2 vs phase 3?

Everyone keeps quoting 48 weeks at 19.1%, which honestly makes it a phase 2 dropout with good PR.

The scale called me a failure for nine days, then my jeans fell down. Trust the tape too.

My week 30 to 40 stall turned out to be sleep, not food: I was averaging 5.5 hours and 4k steps, then got back to 7.5 hours and a 45-minute after-dinner walk, and the scale moved 7 lbs over six weeks. If phase 3 sites had better sleep/step coaching, that alone could explain part of the 28.7 vs 24.2 gap. How was your sleep and step count during weeks 30 to 40?

28.7% smells like completers-only math; were the Phase 3 withdrawals counted the same way as Phase 2?

I stopped chasing headline percentages after my 7-day average hid a 4-lb salty weekend. I track navel waist and a monthly photo; scale was down 21% at week 48, but waist was down 5.5 inches. The 28.7 vs 24.2 gap could just be different baseline BMI or adherence rules, not a new step change.

My 28.7-style whoosh was just water: one salty weekend erased 3 lbs, then it came back by Wednesday.

Your 231 to 189 is about 18.2%, so you're already closer to the Phase 2 mean than it feels. I added 8k steps and two 20-minute dumbbell circuits at week 36; my 12-week rate went from 0.7 to 1.1 lb/week without changing meals much. Trial lifestyle support may explain part of the 28.7 gap.

Week 30 broke my brain: scale flat 10 days, then down 3.2 lbs by day 14.

Sleep was my weird lever: weeks 3–11, at 7.5 hours I averaged 1.1 lb/week, at 5.5 hours only 0.4. The reversal was that forcing 8 hours made me anxious and snacky; 7.5 plus a 20-minute after-dinner walk fixed my evening cravings beter than any food swap.

The 28.7 is a protocol mean, not a promise for what week 48 looks like in real life. What broke a long flat stretch was adding 3x/week squats and rows for 6 weeks: scale flat, navel tape down 1.5 inches, shirts went L to M. Waist measured weekly, same spot every time, before trusting any headline.

My 48-week marker was stairs: stopped twice at week 4, zero stops by week 40.

Weekends wrecked me: Friday pizza plus Sunday brunch held 3 lbs water until Wednesday.

I only trust monthly averages; daily weigh-ins made me nuts, so I log 7-day median.

My waist dropped 4 inches before scale moved again at week 30; clothing fit beat trial percentages.

My gym parking spot farthest from door added 1200 steps daily; scale finally moved week 27.

the 4.5-point gap is probably estimand + adherence, not a different drug. Phase 3 often reports treatment-regimen numbers with more protocol support; Phase 2 can be intent-to-treat with more early dropouts. Read the SAP, not the slide: missing-data rule, estimand, baseline BMI/A1c mix. My own optimization: I track a 14-day EMA slope plus a weekly adherence score (protein, sleep, stress), not headline percentages. Your 231→189 is ~18.2% at 48 weeks; still solid. What’s your weekly slope over the last 8 weeks? If it’s still negative, trial means are context, not a ceiling.

hi, total newbie here—week one, so I’m mostly lurking and taking notes. One thing that’s helping my nerves is tracking 7-day rolling averages for weight and fasting glucose instead of daily numbers; the daily jumps were making me squirrelly. Genuine question for OP: did your fasting glucose come down steadily with the weight, or did it drop in a chunk after a certain week? I’m trying to learn what to expect beyond the scale, and glucose seems like the quieter win nobody posts about. Also, congrats on 48 weeks of logging—that consistency is impressive.

I’d stop comparing your n=1 to trial means and compare slopes instead. Trials give a group average at 48 weeks; you’ve got 48 weekly points. I track fasting glucose CV and grip strength to catch lean-mass loss before the scale gets weird. Mine: glucose CV fell from 13% to 9% while weight was flat for six weeks. Sharp question: do the Phase 3 readouts include body-composition sub-studies, or just total weight? If it’s only weight, 28.7% is a marketing number, not an outcome I can optimize against.

I did the same math when I hit 48 weeks: 44 lbs off 240 was ~18%, but my body-fat scale said lean mass stayed flat while fat dropped more. Trials report mean percentage change, not median, and a few big responders can pull the mean. Also, if you started at 231 and are shorter, your baseline BMI may be lower than the trial average, so 24% is simply a bigger ask. What’s your height/starting BMI? Did you track body fat or lean mass at all?

Check the CTgov results tables yourself. Phase 3 “up to” usually means highest treatment group and/or completers. Phase 2 24.2% is often the all-randomized mean. Different denominators.

Baseline BMI also matters. 231 at 5'4" is a different percentage than at 6'0". Your 42 lbs is 18.2% from baseline.

Night shift can mess with sodium and glycogen, so

One concrete thing I’d check: whether those percentages are ITT vs completers/efficacy estimand. Headline “up to” numbers often come from a secondary endpoint in a specific arm, not everyone randomized. I quit comparing my n=1 to trial means and instead run a 4-week rolling

Not a scientist, but I travel 40 weeks/year and track in spreadsheets. One thing that jumped out: Phase 2 vs 3 usually differ in baseline BMI and how much support/phone check-ins people get, not just the med. My hotel/airport weeks always flatten my curve because sodium and sleep tank, then whoosh at home. If the Phase 3 sites had more frequent visits, that alone could explain several points. Do you know if the 28.7% is completers or everyone randomized? That’s my nerd question.

One thing I’d dig into: whether the Phase 3 28.7% is an on-treatment/completers number while the 24.2% is intent-to-treat. Those aren’t apples-to-apples, and dropout patterns alone can create that gap. Also check baseline BMI—percent loss from a higher starting weight often looks bigger even at the same absolute pounds. For your n=1, I’d keep separate columns for weekly average, waist, and fasting glucose so a stall in one doesn’t hijack the story. Does the 28.7% source say how missing data were handled? That’s the first thing I’d look for.

One thing that helped me: check whether those % are “all randomized” or “completers,” and whether they’re on-treatment vs treatment-policy. That alone can swing a few points. Also baseline BMI and diabetes status matter—if Phase 3 had more people starting at higher BMI and fewer with T2D, the mean looks bigger even with the same medication. Your 231→189 is ~18%, but A1c 5.8→5

i’m just a dorm rat tracking Greek yogurt macros, so take this with salt, but the number I’d check is baseline BMI and diabetes status. If Phase 2 had more T2D or different starting weights, 24.2 vs 28.7% isn’t apples-to-apples. Did you compare the baseline characteristics tables and whether they adjusted for BMI/A1c? Also, “% of starting weight” means a 300-lb person can

I’d chase baseline BMI/diabetes duration before the headline %. Phase 2 often has more T2D and lower starting BMI; Phase 3 can skew heavier and longer on treatment, which alone shifts % weight loss. Also check if 28.7% is total weight or fat mass. In my n=1, lifting 4x and protein near 1g/lb made scale loss slow but waist and DEXA fat% dropped faster. If Phase 3 used DEXA/waist, that’s a different animal. Do you know whether the Phase 3 endpoint is total body weight or fat mass?

For what it's worth, we beat this around in the old “forest plots for normal humans” thread: before comparing 24.2 vs 28.7, I’d look at baseline BMI and diabetes status. A cohort starting at 38 BMI can post a bigger mean % than one starting at 34, even with similar absolute pounds lost. Your 42 lb drop is ~18% of 231, which is solid. Do you know the baseline mean weight/BMI for NCT05882045? Also, were those Phase 3 arms running alongside a lifestyle program? That stuff can move a few points without any real drug difference.

One thing I’d look at is baseline BMI and median, not just mean. Percent loss flatters higher starting weights, so someone 300 lbs dropping 60 is 20%—same as your 231→189 at 18%. If the Phase 3 group had more

one thing I’d check before the headline %: the exact timepoint and estimand. “Up to 28.7%” might be week 72, while the Phase 2 24.2% is week 48 — not apples-to-apples. Also, do the large trials report discontinuation rates? A few points can come from missing-data handling alone. I’m just a 50-something empty-nester with a spreadsheet, but my own 48-week loss stalled on the scale while my waist kept shrinking after I added two short strength sessions and more walking. Are you logging waist/measurements too, or just weight and labs?

I’d dig into baseline BMI and whether there was a diet/exercise run-in before randomization. A 28% mean in a heavier cohort can be the same pounds as 24% in a lighter one, so the % can look like a gap when absolute lbs are close. Also, some programs use a structured lifestyle component throughout, which can widen Phase 3 vs Phase 2 almost by itself. Gentle question: did your loss curve flatten at a specific week, or was it still trending down? I found tracking weekly % rather than lbs helped me see my own plateaus without panicking.

I’d also check whether those trial percentages are means vs medians, and what baseline BMI the trials enrolled. A 24–29% mean can hide a long right tail; median loss often sits a few points lower. Your 42 lb from 231 is ~18%, so if your starting

Night shift here too. Don't chase trial percentages with your numbers. 231 to 189 is 42 lb. That's 18% of your starting weight. 28% would've been ~65 lb. Trial averages also mix baseline BMIs. A 24% mean in people starting at 300+ lb is a different beast. What was your baseline BMI? Also, scale goes sideways on nights. I track waist, fasting glucose, and how clothes fit. Those moved before the scale did. None of that tells you what your next 12 weeks look like.

Not a stats whiz, but the thing I’d chase is baseline weight and the responder breakdown. Percent loss is denominator-dependent—42 lbs off 231 is ~18%, but that same 42 off 260 is only ~16%. If the Phase 3 group started heavier, the headline % can look bigger without anyone losing more absolute pounds. I’d also want the share of people hitting ≥20% or ≥25%, not just the mean, because means can hide a wide spread. Does the Phase 3 supplement list baseline BMI and those responder proportions? That would tell you more than the top-line 28.7% vs 24.2%. (Small-town pharmacy brain just wants it in a simple table!)

Percent weight loss is slippery. Baseline BMI matters. 28.7% off 330 lbs is ~95 lbs. 24.2% off 230 lbs is ~56 lbs. Same med, different folks, different headline. Ask whether Phase 3 had more baseline BMI 35+ or more T2D. Night shift guy here: my scale swings 3–4 lbs after bad sleep or salty food. I track 7-day averages, not single mornings. What was your baseline BMI? And are you comparing your 18% drop to trial means, or to your own 4-week trend? That’s the number that actually matters.

Your 42 lb / ~18% at 48 weeks is a huge win — don’t let trial stats eclipse that. One thing I’d check: the Phase 3 28.7% may be a week 68/72 endpoint, not 48. Also, phase 3 protocols often include a structured lifestyle arm — food logs, activity goals, regular check-ins — while phase 2 can be looser. That alone can shift results. What did your weekly average look like around weeks 20–30? That’s where I’d look for stalls vs. whooshes. Are you tracking protein and steps, or mainly calories?

I track weekly averages too, and what helped was comparing rate of loss rather than only the 48-week number. Trial averages can shift a lot based on baseline BMI and diabetes status, so I’d check whether the Phase 2 and Phase 3 groups looked similar on those. Your 42 lb loss is about 18% of starting weight—meaningful, even if it trails the trial means. If you read the CT.gov entries, are you looking at mean change from baseline or a model-based estimate? That distinction often explains a few percentage points without any real contradiction.

First, 42 lbs and A1c 5.8→5.4 is a huge real-world win — trial means don’t capture how your clothes fit or fasting glucose. One thing I’d check that hasn’t been mentioned: are you comparing week-48 “everyone randomized” numbers vs only people who stayed on treatment? Company Phase 3 releases often spotlight completers or a specific estimand, while peer-reviewed Phase 2 usually reports the more conservative number. Also, did either trial include a diet/exercise run-in or mandatory lifestyle program? If so, the headline % is partly the program. What’s your protein and step count looking like lately?

Data-nerd angle: before the peer-review debate, I’d compare the baseline characteristics tables. Phase 2 vs Phase 3 can differ a lot in starting BMI, % with T2D, age, sex, and how much behavioral support everyone got. A 260-lb starter can hit a bigger % loss than a 231-lb starter with the same absolute pounds, and diabetes status often blunts weight response. Also peek at whether there was a run-in or lifestyle program in one but not the other. Do the CTgov posted results show baseline BMI and diabetes subgroup? That’s the first place I’d look for the 24.2 vs 28.7 gap.

Empty-nester here, tracking my own 48-week spreadsheet too. The angle I’d add: look at discontinuation/adherence, not just baseline BMI. If 10–20% stop early, ITT vs completers-only can swing the headline by several points, and Phase 2 vs Phase 3 often handle that differently. My own curve bent when I added after-dinner walks and started cooking more fish/beans, then flattened during a 3-week grandkid visit. So what were the discontinuation rates in NCT05882045 and NCT05929066? That might explain part of the 28.7 vs 24.2 gap.