GLP-1 Titration Schedule & Dosing Optimizer

Semaglutide (Ozempic, Wegovy) is injected once weekly on the same day each week. The ~7-day half-life documented in the semaglutide population PK analyses (Pratley/Drucker) allows stable plasma levels on weekly dosing. Inject at any time of day, with or without food — the priority is consistency.

Tirzepatide (Mounjaro, Zepbound) follows a weekly injection schedule anchored in the SURPASS and SURMOUNT trial programs. Start at 2.5mg weekly for 4 weeks, then increase to 5mg. Continue escalating every 4 weeks through 7.5mg, 10mg, 12.5mg, to a maximum of 15mg based on tolerance and response.

Four weeks minimum — and the reason is pharmacokinetic, not arbitrary. Semaglutide has a ~7-day half-life, so plasma levels need roughly two half-lives (~14 days) to stabilize after a dose change, and the GI response to that new steady-state concentration can arrive another week or two after. Step up faster than 4 weeks and the nausea from dose N can land after you have already moved to N+1, stacking side effects from two escalations. The STEP and SURMOUNT titration schedules are built around this — 4 weeks is the floor, and extending to 8 weeks when GI symptoms have not settled is the canonical move.

If you miss a dose and it has been less than 5 days (for weekly dosing), take the dose as soon as possible. If more than 5 days have passed, skip the missed dose and take the next dose on your regular day. Do not double up doses.

Yes — and the mechanism is sound. Most GLP-1 side effects track peak plasma concentration: nausea, GI distress, and the motivational flattening people describe as fatigue or anhedonia all scale with how high the post-injection peak climbs. Splitting a weekly dose into two halves (e.g., 2.4mg semaglutide → two 1.2mg injections 3-4 days apart) lowers the peak and raises the trough, which reduces side effects at the top of the cycle and keeps appetite control more consistent at the bottom. This is off-label relative to the labeled weekly schedules, but it is pharmacokinetically coherent for peptides with 5-7 day half-lives. For the full fatigue mechanism and when splitting tends to help most, see GLP-1 Fatigue.

There is no pharmacokinetic basis for a specific hour — with a 5-7 day half-life, the plasma curve is flat enough that a few hours one way or the other does not meaningfully shift exposure. What timing can do is synchronize the peak-to-nadir window with sleep versus active hours. Tmax lands roughly 24-72 hours post-injection, so injecting in the evening means the peak rises overnight and you sleep through the worst of the nausea window; injecting in the morning means the peak overlaps your active day, which is fine if nausea is not an issue and frustrating if it is. Pick the half of the day where you most want the peak to be absent.

Increase your dose when: 1) You have completed 4+ weeks at current dose, 2) Side effects have stabilized, 3) Appetite suppression is weakening or weight loss has stalled for 2+ weeks, 4) You have not reached your target weight. Do not increase if you are still losing weight or experiencing significant GI symptoms.

Semaglutide, tirzepatide, and retatrutide each have their own taper range — cold-turkey at peak dose sets up regain because ghrelin rebounds and the lean-mass loss is already baked in. The working approach is 8-12 weeks at a low maintenance dose (0.25-0.5mg sema, 2.5-5mg tirz, 2-4mg reta) while resistance training and protein lock in. See the semaglutide, tirzepatide, and retatrutide dosing pages for the per-compound taper schedule.