Published-trial titration record
Semaglutide: published trial titration schedule
Semaglutide is available in three MHRA-licensed forms with distinct dose schedules. Wegovy uses a 16-week titration to 2.4 mg weekly subcutaneous (STEP-1 schedule). Ozempic titrates to 1 mg or 2 mg weekly. Rybelsus is the only oral GLP-1 — 14 mg daily after a 60-day titration, with strict empty-stomach administration. Dosing schedules differ; the molecule does not.
Trial anchor
STEP-1 (NEJM 2021, PMID 33567185) for the Wegovy schedule; SUSTAIN-6 (NEJM 2016, PMID 27633186) for the Ozempic CV-outcomes context.
Full molecule profile: Semaglutide
Published titration schedule (trial record)
| Step | Trial-arm dose | Notes |
|---|---|---|
| Week 1-4 | 0.25 mg weekly s.c. (Wegovy) | Initiation only; non-therapeutic. |
| Week 5-8 | 0.5 mg weekly | Ozempic licensed maintenance starts here for some patients. |
| Week 9-12 | 1.0 mg weekly | Ozempic primary maintenance dose for T2DM. |
| Week 13-16 | 1.7 mg weekly | Wegovy intermediate step. |
| Week 17+ | 2.4 mg weekly (Wegovy maintenance) | STEP-1 endpoint dose — ~15% mean weight reduction over 68 weeks. |
Maintenance phase (as reported)
Wegovy is licensed for indefinite maintenance at 2.4 mg weekly. Ozempic is typically maintained at 1 mg or 2 mg weekly for T2DM. Rybelsus is 14 mg daily orally — taken on an empty stomach with no more than 120 ml plain water, 30 minutes before food or other oral medication.
Route & storage (trial protocol)
Subcutaneous prefilled pen (Wegovy / Ozempic) or oral tablet (Rybelsus). Pens stored at 2-8°C; up to 28 days at room temperature (≤30°C) once in use. Rybelsus tablets stored at room temperature in original blister packaging.
Missed-dose handling (trial protocol)
Wegovy / Ozempic: if more than 48 hours have passed since the scheduled dose, skip and resume the next week. Within 48 hours, administer the missed dose. Rybelsus: take the missed daily dose the next day; do not double up.
Methodological considerations
- Insulin / sulphonylurea: hypoglycaemia risk — those agents typically reduced.
- Diabetic retinopathy: rapid glycaemic improvement can transiently worsen retinopathy; monitor at baseline.
- Pregnancy: contraindicated. Discontinue ≥2 months before planned conception.
- Severe gastroparesis: contraindicated.
What this evidence does not prove
- · A published titration arm is not a prescription, recommendation or self-administration guide.
- · Trial-arm doses apply only within the studied population, comparator, duration and primary endpoint.
- · Individual suitability requires qualified clinical assessment where licensed; investigational compounds require authorised research oversight.
- · Off-label, compounded, grey-market or self-supplied versions of the same active ingredient may have substantially different identity, purity, sterility and pharmacokinetics.
FAQs
- Why does Rybelsus use 14 mg daily when Wegovy uses 2.4 mg weekly?
- Oral semaglutide has limited bioavailability (~1%) because the gut absorbs only a small fraction even with the SNAC absorption-enhancer formulation. The 14 mg daily oral dose is calibrated to deliver pharmacologically meaningful plasma exposure roughly comparable to 1 mg weekly Ozempic — not the higher 2.4 mg weight-management dose. Wegovy is not available orally.
- Why a 16-week Wegovy titration when Ozempic titrates over 8?
- The higher 2.4 mg Wegovy endpoint dose produces substantially more gastrointestinal effect than the 1 mg Ozempic endpoint. The longer 16-week schedule was developed in STEP-1 to manage that intensification — keeping discontinuation rates around 4-6% rather than the much higher rates that compressed titration would produce.
- Is semaglutide compounding legal in the UK?
- Compounding of MHRA-licensed semaglutide for an individual patient by a registered UK pharmacy under prescriber authorisation is permitted, but the compounded product is not the same regulated medicine — purity, sterility and stability are the pharmacy's responsibility. Bulk compounding for general supply is not permitted.