Week 20 labs: ALT crashed, glucose barely moved — glucagon?

ALT 41 to 22 at week 20 is wild. Mine went 38 to 31 by week 16, but weight loss was only 6%. Did your triglycerides move early or late?

Trigs fell by week 12, bfeore much scale change. Liver panel stayed flat until week 18. Timing is messy.

The timing mismatch is why I doubt it's just weight loss. My ALP went up though, which nobody warned me about.

Mine was transient, around 12 U/L. Clinician wasnt worried.

I get the glucagon angle, but I'm not convinced. At my site, people with more early nausea seem to lose faster, which could just mean lower intake. Your ALT drop might still track visceral fat even if BMI loss looks modest. Did your waist change more than weight? My waist fell 7 cm while scale only moved 5%, yet liver enzymes didn't drop until week 22. Also, are you fasting for those draws? My triglycerides swing 30 points if I slip on the fast. The ALT number is striking, though, so I'm not dismissing your hunch.

Waist mattered more for me too. Down 6 cm.

MRI-PDFF substudy would answer this better than our n=1 guesses?

Week 16 here, scale stuck at -8.2% for 26 days but my belt went in two notches and ALT fell 36→19 while trigs dropped 172→118, so the out-of-proportion labs thing rings true. The twist for me was that those numbers tracked sleep and weekend drinks way more than the scale — I went from 4-5 beers across Fri/Sat to one, and started a 20-25 min after-dinner walk, and my next draw looked totally different. Fasting glucose, though, stayed parked at 99-101 and A1c only moved 5.7→5.6, which was weirdly stubborn. If you're already doing the obvious stuff, maybe look at whether the prior draw was after a bad sleep week or a few drinks, because that can make a single ALT swing look bigger than the fat loss. Are your waist or how your jeans fit changing at all, or is it purely scale and labs?

My ALT went from 38 to 19 by week 14 and I’m convinced it was the booze, not the weight — I cut from 6 drinks/week to basically zero and my trigs went from 170 to 98 in the same window while my scale only moved 4%, so I’d look at anything else that changed in your routine around week 16-18 before crediting the drug’s mechanism. I track labs in a spreadsheet and my liver numbers always lag the scale by about a month, so if your glucose is still sitting at 96 at week 20, I’d bet your week 24 draw shows it finally dropping — that’s been the pattern for me, slow A1c, fast ALT.

late-night gamer here. my soda-swap experiment: cut regular soda at 2am, went sparkling water instead, and my fasting glucose didn’t budge for weeks. cgm showed the “dawn” spike was really from gaming till 3am, not meals. did your week20 panel include a1c or fasting insulin? glucose alone can look stuck while other stuff shifts. also curious if your sleep timing changed between draws, since that moved my numbers more than the scale did.

Curious whether the glucose endpoint in that cohort is fasting glucose or A1c, because those can tell different stories. My n=1: ALT fell before my fasting glucose budged at all; the only thing that moved my morning number was a 10-min walk after dorm carbs. Cheap-protein swap that helped me: cottage cheese + frozen berries instead of cereal/milk. Similar protein, way less post-meal crash, and it fits a mini-fridge. But yeah, without CGM data I’d be cautious blaming glucagon from group averages.

Mechanism-wise, if glucagon tone is up, I’d want fasting insulin or HOMA-IR, not just glucose. In the trials, a flat fasting glucose with falling weight could still hide better hepatic insulin sensitivity if endogenous glucose output is offsetting it. Did the extension report C-peptide or ketones? I track fasting glucose and BHB at home, and mine often split—glucose barely moves while ketones creep up in a bigger deficit. Curious if that pattern showed up in the cohort.

Night shift here: blind or not, my labs are still guessing too.

I log my lab dates next to sleep, steps, and alcohol-free days, and my ALT swings have tracked way more with a dry month + daily walks than with the scale. So I’d want the extension’s liver-fat/PDFF or GGT data, plus waist circumference, not just ALT and weight. ALT crashing while glucose barely budges seems more like visceral/liver fat mobilization than glucagon tone to me. Was the 9.6% at week 20 total weight or fat mass, and did they report the draw timing relative to the week-20 visit?

helpful context. One concrete question: does the extension report whether participants had elevated ALT or MASLD at baseline? If not, a week-20 ALT drop could partly be regression to the mean. In my own tracking, ALT follows my weekly weight average more than any single lab day, while fasting glucose often lags by a few weeks. I also mark any strenuous workout within 48 hours of the draw, because that has changed my values before. Wishing you steady progress.

Curious whether the extension stratifies by baseline ALT or hepatic fat. In trials, ALT drops often look bigger than glucose changes, but it’s hard to know if that’s direct

Question for the trial watchers: does that extension report anything after the treatment period ends—washout or maintenance follow-up? That’s the part I care about now that I’m maintaining. During active loss my ALT bounced around, but

The glucagon mystery is above my snack-drawer pay grade, but I’m following!

i’m more curious about the glucose side tbh. did that extension use cgm data or just fasting/a1c? my own soda-swap n=1 was weird: zero sugar at night dropped my fasting numbers but post-dinner spikes stayed ugly till i stopped late-night cereal lol. if they only report fasting glucose, feels like the glucagon-ish stuff could hide in the post-meal curve. anyone tracking both?

blind is blind. Anecdotes are just guessing. Night shift brain approves.

ALT falling early often tracks liver fat loss more than glycemic change. In my own labs, ALT normalized a good month before fasting glucose got boring-flat, and it only moved after my waist trend did. So if the extension is reporting ALT without liver fat imaging (MRI-PDFF, PDFF change, or even FibroScan), I’d treat the glucagon angle as interesting but not settled. Do they have any liver-fat endpoint buried in the supplementary materials?

Blind is blind—meanwhile I’m just guessing airport salad macros. Following! ✈️

Hi, total newbie here (day 5), so forgive the basic question: was the glucose endpoint fasting plasma glucose, HbA1c, or HOMA-IR? I’ve only just started tracking, but my fasting number swings more with sleep than food, which makes me wonder if stress/sleep could muddy 20-week comparisons. Also, did the extension report anything on lan mass or waist-to-height? The 9.6% weight loss is interesting, but I’d love to know if the composition changes explain the lab split.

I track a CGM and my fasting glucose is always the last thing to budge; post-meal spikes improve first. So when I see “glucose barely moved,” I want to know if that’s fasting, 24h mean, or postprandial. If it’s fasting, the glucagon angle feels more plausible to me. If it’s mean, maybe the weight loss just hasn’t hit that lever yet. Did the extension report CGM data or just fingersticks?

night shift here too. My glucose is always the last lab to budge. Annoying.