Weeks 1 to 4: the initiation dose

The first month has one job in the label: get you used to the medicine. Everything else is a side effect of that job, good and bad.

What the label says this month is for

Wegovy: "0.25 mg once weekly for 4 weeks" as the first step of the escalation schedule, which the label says is used to reduce gastrointestinal adverse reactions (section 2.1). Zepbound: 2.5 mg once weekly for 4 weeks, described as being for treatment initiation and not approved as a maintenance dose (section 2.1). Neither label attaches a weight figure to the initiation dose, and none of the pivotal trials had an arm that stayed on it. The tirzepatide hub has the same point in more detail for that molecule.

What is happening in your blood

Each weekly dose lands on what is left of the last one. Semaglutide has a half-life of about a week, so after the first injection about half is still there when the second arrives, and the level climbs until intake and clearance balance at steady state, which the label puts at 4 to 5 weeks (section 12.3). Tirzepatide's half-life is about 5 days and steady state is about 4 weeks. Practically: week four feels like more drug than week one at the same dose, which is the reason the label holds every step for at least four weeks before deciding on the next.

Side effects: what, and when

The labels report adverse reactions over the whole trial, not by week, so no honest table says "week 2: 30% nauseous". What they report:

Two things about timing that the labels do state. Wegovy: most gastrointestinal reactions were mild or moderate and most occurred during dose escalation. Zepbound: nausea, diarrhea, vomiting and constipation occurred more often during dose escalation and decreased over time. Weeks 1 to 4 are the first escalation stretch. The trial papers add the shape: in STEP 1 nausea and diarrhea were "typically transient" (PubMed 33567185); in SURMOUNT-1 gastrointestinal events were mostly mild to moderate and occurred primarily during dose escalation (PubMed 35658024).

Read the table the other way too. 56% of people on Wegovy did not report nausea. 71 to 75% on Zepbound did not. Feeling fine is not a sign the drug is not working.

Appetite

Reduced appetite is the effect, not a side effect, and it usually arrives before any weight change you can measure. The practical problem it creates is under-eating and under-drinking, which are the road to the dehydration and kidney warnings in the label. Two pages cover it: eating when you have no appetite and hydration. Protein first, fluids on a schedule, small plates.

The scale

Weigh yourself once a week if you want a record, on the same scale at the same time. Do not use the number to judge the drug this month. The published curves start separating from placebo at the first measurement point, week 4, and keep falling for a year or more (when weight change starts). Week 2 is not in the data.

Do not accelerate

The one mistake with consequences in this stretch is moving to the next dose early. The labels require four weeks at each step, and FDA's page on unapproved GLP-1 products describes adverse events where compounded dosing ran ahead of the label schedule. If week three is easy, that is good news for week five, not a reason to skip to it.

Checklist for the end of week 4

• Four injections done on the same weekday, sites rotated.
• Your one-line weekly log has four lines.
• You know whether your prescriber wants a check-in before the first increase (most do; the label expects tolerability to be assessed).
• You have the next strength in hand, or know when it arrives.
• You have read weeks 5 to 8.