Weeks 5 to 8: the first step up

Week 5 is the first time the plan changes. The label ladder moves from 0.25 mg to 0.5 mg for semaglutide and from 2.5 mg to 5 mg for tirzepatide (section 2.1 of each label). For tirzepatide that second step is also the lowest dose the Zepbound label calls a maintenance dose, and the lowest dose that had its own arm in SURMOUNT-1.

The decision comes first

The increase is not automatic. The label expects the prescriber to consider how you tolerated the previous four weeks before increasing, and many programs require a check-in before shipping the next strength. Bring your one-line log. If weeks 1 to 4 were easy, the increase is routine. If they were rough, the labels give the prescriber room: the Wegovy label allows delaying an increase by four weeks if a step is not tolerated, and after a step up to 2.4 mg allows a temporary return to 1.7 mg (section 2.3); the Zepbound label says to consider delaying escalation if a dose is not tolerated. Holding at the current dose is a label option, not a failure.

Why it can feel like week one again

The blood level had just reached steady state at the old dose. A higher dose starts a new climb toward a new steady state, four to five weeks out (section 12.3). The side effects that follow a rising level, mostly nausea, come back for some people in the first days after the first higher-dose injection, then settle. Both labels place gastrointestinal reactions predominantly in escalation. The pattern of a day or two around the peak, then improvement by the next injection, is the same as in weeks 1 to 4; the difference is that this time you know what it is.

Constipation is the reaction more likely to build rather than pass. It appears in 24% of people on Wegovy versus 11% on placebo, and 11 to 17% on Zepbound versus 5% (section 6.1). Fluids and fibre are the first line; the hydration page has the label reasoning. Severe constipation with abdominal pain, bloating and vomiting is a different thing (the labels list ileus among post-marketing reports) and belongs on the call list.

Appetite and food

By this point most people have noticed the appetite change and some are eating a great deal less than they realise. This is the stretch where protein intake and fluids need to be deliberate. Eating when you have no appetite has the approach. If you find yourself skipping meals entirely, that is worth mentioning at the check-in; the label warnings on dehydration and acute kidney injury are about exactly this.

What the trials measured here

Both pivotal trials weighed participants at week 8. In STEP 1 the semaglutide curve was already clearly below placebo at that visit and continued down through week 68, ending at a mean 14.9% reduction against 2.4% (PubMed 33567185, Figure 1). In SURMOUNT-1 the three tirzepatide curves were below placebo by week 8 and kept falling to 15.0%, 19.5% and 20.9% at week 72 against 3.1% (PubMed 35658024, Figure 1). The figures show a slope, not a plateau, at week 8: most of the total change in both trials came later, during and after the rest of escalation. When weight change starts puts the curves side by side.

If you are on a compounded product

The 0.5 mg or 5 mg step means a different number of syringe units from the same vial, or a new vial at a different concentration. Recalculate with the dose unit converter and confirm with the pharmacy before the first draw at the new dose. Compounded products are not FDA approved and are not interchangeable with brand pens; the schedule you follow is your prescriber's, and the label ladder here is orientation only.

Checklist for the end of week 8

• Prescriber confirmed the step; you know the plan for week 9.
• Log has eight lines, including how the step-up week compared with week 1.
• Fluids on a schedule, protein at every meal.
• You have read the when to call page again with fresh eyes; the gallbladder and pancreatitis symptoms matter more as weight starts to change.