FDA approves reformulated oral semaglutide tablets in three new strengths

On December 9, 2024, the FDA approved a reformulated version of Rybelsus (semaglutide) tablets for adults with type 2 diabetes, adding three new tablet strengths — 1.5 mg, 4 mg and 9 mg — along with instructions for switching between the new tablets and the older ones ^[1][3].

The decision covers two supplemental applications to Novo Nordisk's original application, NDA 213051, submitted to the FDA on February 9 and June 6, 2024 ^[1]. The first supplement, S-020, covers the new formulation, called R2, its recommended dosing, and recommendations for switching between the original R1 tablets and the R2 tablets ^[1]. It also adds a manufacturing site: Novo Nordisk Pharmaceutical Industries in Durham, North Carolina ^[1].

The original Rybelsus tablets, first approved September 20, 2019, come in 3 mg, 7 mg and 14 mg strengths ^[3]. The two formulations are not interchangeable milligram for milligram. Current labeling states that Rybelsus and Ozempic tablets "are not substitutable on a mg-to-mg basis" ^[5].

The second supplement, S-021, updated the lactation section of the prescribing information with results from trial NN9924-4669, which measured semaglutide and salcaprozate sodium (SNAC) levels in the breast milk of healthy lactating women after multiple doses of oral semaglutide ^[1]. That trial was run to satisfy a postmarketing requirement set when the drug was first approved in 2019 ^[1]. The label says breastfeeding is not recommended while taking these tablets ^[5].

During the review, the FDA also made safety labeling changes. The terms "dysesthesia" and "alopecia" were added to the clinical trials experience section of the prescribing information ^[1]. The approval letter does not give rates for either, or say how long they lasted. A new "Severe Gastrointestinal Adverse Reactions" warning was added to the warnings and precautions section to bring the label in line with other GLP-1 receptor agonists ^[1]. The FDA also made editorial revisions to the acute pancreatitis section for clarity and revised the Medication Guide ^[1].

The most common adverse reactions, in at least 5% of patients, remain nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation ^[5]. The tablets carry a boxed warning about thyroid C-cell tumors seen in rodents and are contraindicated for people with a personal or family history of medullary thyroid carcinoma or with MEN 2 syndrome ^[5].

On the pediatric side, the FDA waived the study requirement for ages 0 through 9 because too few children in that age range have type 2 diabetes, and deferred the requirement for ages 10 to 17 ^[1]. The pediatric study's completion is scheduled for December 2026, with a final report due June 2027 ^[1].

Why it matters for patients

There are now two sets of oral semaglutide tablets with different numbers on the label, and they cannot be swapped milligram for milligram ^[5]. The prescribing information sets out separate starting and step-up schedules for each, and separate instructions for switching between them ^[5]. Someone moving from one product to the other is not simply taking the same pill under a new name — the milligram strength changes, and a pharmacist filling a prescription may dispense a different number than before.

The naming has also changed since approval. On January 30, 2026, the FDA approved a labeling update renaming the R2 tablets from Rybelsus to Ozempic (semaglutide) tablets ^[3][5]. Rybelsus now refers only to the 3 mg, 7 mg and 14 mg tablets ^[5]. That means the same once-daily pill can arrive under a brand name that also refers to a once-weekly injection, which is a different product with a different schedule ^[2][5].

Dysesthesia, a term for unusual sensations such as burning or tingling, and alopecia, or hair loss, now appear in the clinical trials experience section ^[1]. How often they occurred, whether they were mild, and whether they went away after stopping the drug have not been disclosed.

The newly added severe gastrointestinal warning is also worth knowing about: the label states that gastrointestinal reactions, sometimes severe, have been associated with these tablets, and that they are not recommended for people with severe gastroparesis ^[5].

What happens next

The December 2024 letter set deadlines for the company: updated labeling in structured product labeling format within 14 days, and final printed carton and container labeling within 30 days after printing ^[1].

The pediatric study in children and adolescents ages 10 to 17 with type 2 diabetes is scheduled to finish in December 2026, with the final report submitted in June 2027 ^[1].

Several changes have already followed. Rybelsus was approved for cardiovascular risk reduction in adults with type 2 diabetes at high risk on October 17, 2025 ^[3]. Wegovy tablets, in 1.5 mg, 4 mg, 9 mg and 25 mg strengths, were approved December 22, 2025 ^[3]. And the R2 tablets were renamed Ozempic tablets on January 30, 2026 ^[3][5].