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c/semaglutide·posted 2 years ago by u/nikhil_teixeira

why does nobody talk about semaglutide

Discussion Clean Column ×7 Sourced ×3

why does nobody talk about semaglutide, and I want the answer with the reasoning attached rather than just the conclusion.

The mental model that finally made this click for me: there are two curves, and people watch the wrong one.

The first is exposure, which is set by the dose and smoothed by a week-long half-life. It changes when you change the dose and then settles over about a month. The second is body weight, which is exposure filtered through appetite, food, water, sleep, training and the scale itself, and which moves in steps rather than a line.

Almost every "it stopped working" post is somebody watching curve two over a fortnight and drawing conclusions about curve one. If the appetite effect is still there, exposure is fine. Wait the month.

Dropped my injection day by two days once because of travel. Nothing happened. The panic was worse than the effect.

Kept a log from week one and the single most useful column turned out to be waist, not weight.

I will update this if the picture changes rather than quietly leaving it up.

3,235 up / 958 down77% upvoted55 commentsid 14n5dp5 Jan 2024

55 comments

30 in this archive, depth 6

best — the order this archive was captured in

u/camila_mensa141 points·2 years ago

STEP-1 ran 68 weeks and landed just under 15% mean body weight change on 2.4mg. It is an average of a wide distribution, not a target you have missed.

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u/anya_salgado49 points·2 years ago·edited

Cosigning. The appetite change and the scale change ran about three weeks apart for me too.

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u/vikram_ferreira26 points·2 years ago

STEP-1 averaged just under 15% at 68 weeks, so a 10% year is not a failure

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u/leila_vasquez97 points·2 years ago

Genuine question — is the appetite effect still there, or is it just the scale that has paused?

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u/archived_thread_a65 points·2 years ago

dose day drift of a day either way is fine, the curve barely notices

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u/careful_gradient_again76 points·2 years ago

if 2.4mg is working there is no prize for going up

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u/niels_lindqvist94 points·2 years ago·edited

How long was the stall before you decided it was a stall?

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u/micro_bump_mick22 points·2 years ago

That figure is the 68-week trial mean, not a weekly rate. Dividing it by the weeks gives you a number that does not mean anything.

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u/boots_or_bust-33 points·2 years ago

Week 50: 24kg down, injection-site soreness basically gone since about week 10, and the honest headline is that nothing dramatic happened. It was boring and it worked.

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u/anya_salgado75 points·2 years ago

The weekly interval comes out of the half-life — roughly a week — so you are on a smooth curve rather than a series of spikes. That is also why moving your day slightly does very little.

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u/arne_amankwah42 points·2 years ago

Small correction: 2.4mg is the maintenance ceiling on the label, not the starting maintenance dose. The distinction matters for anyone reading this later.

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u/gustav_solberg49 points·2 years ago

Sceptical of the mechanism you are proposing. Gastric emptying slows, it does not stop, and the timings you describe do not follow from it.

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u/archived_thread_a40 points·2 years ago

2.4 is a ceiling, not a target

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u/sofia_wikstrom75 points·2 years ago

staying at 1.7mg for an extra month is a legitimate plan

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u/titration_marshalMOD100 points·2 years ago

Retitled to match the body. The original promised a comparison the post does not make.

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u/arne_restrepo27 points·2 years ago

Strongly agree on protein. It did more for my injection-site soreness than any of the things I bought to fix my injection-site soreness.

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u/nausea_notesside effects69 points·2 years ago

The escalation schedule in the trials existed to keep people on the drug. It is a tolerability ramp, and it is why the label reads the way it does.

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u/two_mil_or_one69 points·2 years ago

Careful. A four-week stall is inside normal variation and treating it as failure is how people escalate for no reason.

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u/tomas_kimani24 points·2 years ago

the food noise going quiet is the effect people actually describe

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u/joaquin_stanescu12 points·2 years ago·edited

the food noise going quiet is the effect people actually describe

This is the part I would underline for anyone skimming. Everything else in the thread is downstream of it.

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u/nikhil_teixeiraOP4 points·2 years ago

First month I lost almost nothing and nearly quit. Month two and three were where it all happened.

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u/ahmed_okafor2 points·2 years ago

First month I lost almost nothing and nearly quit.

Adding one thing to this: the appetite effect and the scale run on separate clocks, so both halves can be true at once.

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