The first twelve weeks

What this page is

A description of what the pivotal trials did and what members commonly report. It is not a protocol, it is not a recommendation, and it is not tailored to you. Titration is a clinical decision. Several compounds discussed on this site are not approved for human use anywhere.

The schedules the trials used

The published escalation schedules are slower than most people assume, and they are slow for a reason: the terminal dose was the same either way, so escalating faster bought nothing except side effects.

Weeks	Semaglutide (STEP)	Tirzepatide (SURMOUNT)
1–4	0.25 mg	2.5 mg
5–8	0.5 mg	5 mg
9–12	1.0 mg	7.5 mg
13–16	1.7 mg	10 mg
17–20	2.4 mg	12.5 mg
21+	2.4 mg maintenance	15 mg maintenance

Sources: STEP 1 (Wilding et al., N Engl J Med, 2021) and SURMOUNT-1 (Jastreboff et al., N Engl J Med, 2022). Trial schedules were fixed by protocol; real-world escalation is individualised and frequently slower, which is not a failure.

Notice that in both programmes, week 12 is only the third dose step. If you are at the top of the ladder by week 8, you are not ahead — you are outside anything that was studied.

The pattern of the first three months

Weeks 1–2: probably nothing

The starting dose is a tolerability dose. It is not expected to do much. Semaglutide's half-life is around 168 hours, so steady state on any given step takes roughly four to five weeks to establish — what you feel in the first week of a new dose is not what that dose does.

Roughly one post a day on this site is a version of "week two, nothing is happening, is it working". It is the single most common question in c/newbiequestions and the answer is always the same.

Weeks 3–4: something, usually

Appetite effects typically become noticeable here. Many people describe it less as hunger reduction than as the disappearance of the constant background negotiation about food — the thing this community calls food noise. Mild GI effects commonly appear in the same window, usually strongest in the day or two after a dose.

Weeks 5–8: the wall

Early water-weight loss has finished, the scale slows, and enthusiasm drops. The number of people who quit around here is large and mostly unnecessary. Two things help: a seven-day rolling average instead of a daily number, and a measurement that is not the scale — a waist measurement, a clothing fit, a resting heart rate, anything.

Weeks 9–12: the honest baseline

By the end of week 12 most people have a real signal: a rate of change, a side-effect profile, and a sense of whether the dose they are on is doing the job. This is the first point at which "it is not working for me" is a well-founded statement rather than impatience.

Side effects, with trial numbers

GI effects dominated the adverse-event tables in every trial in this class, were mostly mild to moderate, and were mostly concentrated during escalation rather than at maintenance. In STEP 1, nausea was the most frequently reported adverse event on semaglutide 2.4 mg, and discontinuation specifically due to GI events was in the low single-digit percentages — a small number that nevertheless represents real people.

Effect	Typical timing	What members report helps
Nausea	Day 1–3 after a dose, worst on a new step	Smaller meals, stopping at roughly 70% full, sometimes moving the injection to the evening
Constipation	Builds over weeks	Hydration, fibre timing, movement, magnesium — in that order of reported impact
Reflux	Weeks 2–6	Earlier last meal, smaller portions
Fatigue	Escalation weeks	Usually under-eating or dehydration wearing a costume
Sulphur burps	Sporadic	Nothing reliable. It passes.
Resting HR up a few bpm	Escalation	Commonly settles at maintenance; worth tracking rather than guessing

Not a forum question

Severe or escalating abdominal pain, persistent vomiting, signs of dehydration, jaundice, or sudden vision changes are urgent-care questions. Contact a clinician the same day. c/sideeffects locks these threads with a pointer to help rather than letting strangers speculate, and that policy exists because of a small number of posts that should have been an A&E visit.

Get baseline labs before week 1

You cannot go back later and collect a baseline. Six months in, "my ApoB is 84" is a much less useful sentence than "my ApoB went from 118 to 84". The c/bloodwork shortlist is a lipid panel including ApoB, A1c, ALT, a full blood count, ferritin, and renal function — with the caveat, repeated constantly in that community, that nobody on the internet can interpret your results for you.

What the numbers actually were

For calibration, and because these figures get inflated in retellings:

STEP 1 — semaglutide 2.4 mg, mean change in body weight −14.9% at 68 weeks (NEJM 2021).
SURMOUNT-1 — tirzepatide 15 mg, mean change −20.9% at 72 weeks (NEJM 2022).
Retatrutide phase 2 — −24.2% at 48 weeks (NEJM 2023), a phase 2 result and not a phase 3 one.
SELECT — semaglutide 2.4 mg, MACE hazard ratio 0.80 in people with established cardiovascular disease (NEJM 2023).

Three caveats that get dropped every single time these are quoted. They are means, and the individual spread around them is very wide. They sit on top of lifestyle intervention delivered to both arms, and the placebo arms lost weight too. And they are 68 to 72 week figures — at week 12 you are nowhere near them, and you are not supposed to be.

What to include when you ask for help

Posts that get useful answers contain: the compound, the current dose, the week number, how long you have been at that dose, and what specifically changed. Posts that get a template reply contain "is this normal?" and nothing else.

And the rule that applies in every community here: describe what you did, never prescribe to a stranger. Nobody on GLP Research Hub is your clinician, including the people who sound most like one.

Wiki pages are community-maintained summaries, not clinical guidance. If a wiki page and your clinician disagree, your clinician wins.