Titration

What Titration Means

In pharmacology, titration is the process of gradually increasing a medication's dose from a low starting amount to a higher therapeutic target. For GLP-1 receptor agonists, titration is built into every FDA-approved label — patients do not start at the dose that delivers the trial-level weight loss or A1C reduction. They start at a low dose that the gut can tolerate and step up over weeks or months until reaching the maintenance dose where the drug works as designed.

Why GLP-1 Medications Require Titration

GLP-1 RAs slow gastric emptying and act on appetite-regulating regions of the brain. Both effects produce dose-dependent gastrointestinal side effects — nausea, vomiting, diarrhea, constipation, and abdominal pain — that are most intense during the first weeks at any given dose. Titration gives the gut time to adapt to each new dose level before the next escalation.

In the STEP 1 and SURMOUNT-1 pivotal trials, the structured titration schedule was the primary tool for managing tolerability. Without titration, peak-dose nausea rates would likely produce far higher dropout than the 4-7% gastrointestinal-related discontinuation rates actually observed.

Standard Titration Schedules

Each GLP-1 medication has a label-specified titration schedule. The major schedules:

• Wegovy (semaglutide): 0.25 mg → 0.5 mg → 1 mg → 1.7 mg → 2.4 mg weekly, with four weeks at each step (16 weeks to maintenance). Wegovy HD continues to 3.6 mg → 7.2 mg.
• Ozempic (semaglutide): 0.25 mg → 0.5 mg → 1 mg → 2 mg weekly, with four weeks at each step.
• Mounjaro and Zepbound (tirzepatide): 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg weekly, with four weeks at each step (20 weeks to the highest dose).
• Saxenda (liraglutide): 0.6 mg → 1.2 mg → 1.8 mg → 2.4 mg → 3.0 mg daily, escalated weekly (5 weeks to maintenance).
• Foundayo (orforglipron): 3 mg → 6 mg → 12 mg → 24 mg → 36 mg daily oral, with four weeks at each step.

When the Schedule Is Slowed or Paused

Label schedules are recommendations, not mandates. If side effects are severe at a given step, prescribers commonly extend the time at that dose, or step back down to the previous dose and re-attempt the escalation later. The Wegovy and Mounjaro labels both explicitly permit holding a maintenance dose lower than the maximum if the patient is meeting clinical goals and tolerating the current dose well — this is called individualized maintenance.

A slow titration is not a failed titration. Real-world studies consistently show that patients who take longer than the label minimum to reach maintenance have similar long-term weight-loss outcomes to those who escalate on schedule, with fewer treatment-limiting side effects along the way.

Missed Doses During Titration

If a dose is missed during titration, most labels recommend taking it as soon as possible if the next scheduled dose is more than 48 hours away; otherwise, skip it and resume the schedule. Missing more than two consecutive doses at a higher titration step generally requires a return to a lower dose before re-escalating, because GI tolerance partially resets when the drug clears. Patients should never double a dose to make up for a missed one — this concentrates the side-effect burden of the next two weeks into a few days.