Rybelsus (Oral Semaglutide) Titration Protocol
The recommended titration protocol for Rybelsus (oral semaglutide) is to start at 3 mg once daily for 30 days, then increase to 7 mg once daily for at least 30 days, followed by an increase to the maintenance dose of 14 mg once daily if additional glycemic control is needed. 1, 2
Administration Guidelines
- Rybelsus must be taken on an empty stomach with no more than 4 ounces (120 mL) of plain water 3
- Take at least 30 minutes before the first food, beverage, or other oral medications of the day 3
- Swallow tablets whole; do not cut, crush, or chew 1
Detailed Titration Schedule
| Timeframe | Dose | Notes |
|---|---|---|
| First 30 days | 3 mg once daily | Initial starting dose to minimize GI side effects [1] |
| Next 30+ days | 7 mg once daily | Intermediate dose [1] |
| Maintenance | 14 mg once daily | Target therapeutic dose if additional glycemic control is needed [1] |
Special Considerations
Missed Doses
- If a dose is missed, skip that dose and resume the next day at the regular time 3
- For patients who have missed 3 or more consecutive doses, consider restarting the titration schedule 3
- If fewer than 3 consecutive doses are missed and the patient has tolerated the medication well, resuming at the same dose can be considered 3
Ramadan Fasting
- For patients planning to fast during Ramadan, titrate to at least 7 mg approximately 2-3 weeks before Ramadan to ensure therapeutic efficacy and tolerance 3
- Consider dosing at Iftaar (breaking of fast) during Ramadan 3
Renal Impairment
- No dose adjustment is required for patients with renal impairment, including those with severe renal impairment 3
- Oral semaglutide has been studied and found effective in patients with moderate renal impairment 4
Managing Side Effects
Common Adverse Effects
- Gastrointestinal effects are most common: nausea (most frequent), vomiting, diarrhea, abdominal pain, and constipation 3
- Most GI side effects are mild to moderate and transient, typically resolving with continued treatment 5
Strategies to Minimize Side Effects
- Gradual dose titration as outlined above is essential to minimize GI adverse effects 3
- Encourage patients to maintain adequate hydration 3
- Smaller meal portions may help reduce GI symptoms 5
- If severe GI symptoms occur, consider temporarily maintaining the current dose rather than increasing to the next level 3
Monitoring and Follow-up
- Evaluate glycemic response after reaching each dose level 3
- Some patients may achieve adequate glycemic control at submaximal doses (7 mg) and can continue at that dose long-term 3
- If a patient has not lost at least 4% of body weight after 16 weeks of treatment (when used for weight management), consider discontinuation 3
Contraindications and Precautions
- Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 3
- History of pancreatitis (use with caution) 3
- Pregnancy and breastfeeding 3
- Do not use with other GLP-1 receptor agonists or DPP-4 inhibitors 3
- Monitor for hypoglycemia when used with insulin or insulin secretagogues (sulfonylureas); dose adjustments of these medications may be needed 3