From the Guidelines
Semaglutide is available in oral form as Rybelsus, with a recommended starting dose of 3 mg once daily for 30 days, then increasing to 7 mg once daily, and potentially up to 14 mg once daily if additional glycemic control is needed 1. The oral formulation of semaglutide, Rybelsus, is available in 3 mg, 7 mg, and 14 mg tablets.
- Treatment typically begins with 3 mg once daily for 30 days,
- then increases to 7 mg once daily,
- and if additional glycemic control is needed after at least 30 days on the 7 mg dose,
- the dose can be increased to 14 mg once daily. For optimal absorption, Rybelsus must be taken on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day, as noted in the 2024 standards of care in diabetes 1. This strict administration requirement is necessary because semaglutide is a peptide that would normally be degraded in the stomach;
- the oral formulation includes an absorption enhancer (SNAC) that facilitates absorption through the stomach lining,
- but this process is significantly impaired by food or other beverages, as discussed in the context of pharmacologic approaches to glycemic treatment 1. Poor adherence to these administration instructions is the most common reason for inadequate response to the medication, highlighting the importance of patient education and compliance 1.
From the Research
Oral Semaglutide Dose
- The oral dose of semaglutide is available as a treatment option for type 2 diabetes, with a co-formulation of the peptide semaglutide and the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate 2.
- Semaglutide is indicated for use as an add-on combination therapy or as a monotherapy for type 2 diabetes when diet and exercise do not provide adequate glycemic control 2.
- The daily oral preparation of semaglutide has demonstrated clinical effectiveness close to the once-weekly subcutaneous preparation 3.
Clinical Evidence
- Studies have shown that oral semaglutide is well tolerated, with a safety profile consistent with the GLP-1RA drug class, and a low risk of hypoglycemia 2, 4.
- The most common adverse events associated with oral semaglutide are gastrointestinal, with nausea and diarrhea being the most frequently reported manifestations 2.
- Cardiovascular outcome trials have established that semaglutide can reduce various CV risk factors in patients with established CV disorders 4, 5.
Treatment Options
- Semaglutide is available as a monotherapy in both subcutaneous and oral dosage forms, and has been approved as a second-line treatment option for better glycemic control in type 2 diabetes 4.
- GLP-1 receptor agonists, including semaglutide, are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment 3.
- Semaglutide may also be used in combination with basal insulin in either free- or fixed-dose preparations 3.