Rybelsus (oral semaglutide)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved September 2019

Specific Treatments:

adults with type 2 diabetes

Therapeutic Areas

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General Information

Rybelsus is an oral formulation of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist.

Rybelsus is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Rybelsus is supplied as a tablet for oral administration. 

Instruct patients to take Rybelsus at least 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water only. Waiting less than 30 minutes, or taking Rybelsus with food, beverages (other than plain water) or other oral medications will lessen the effect of Rybelsus by decreasing its absorption. Waiting more than 30 minutes to eat may increase the absorption of Rybelsus. Swallow tablets whole. Do not split, crush, or chew tablets.

Recommended Dosage: Start Rybelsus with 3 mg once daily for 30 days. The 3 mg dose is intended for treatment initiation and is not effective for glycemic control. After 30 days on the 3 mg dose, increase the dose to 7 mg once daily. Dose may be increased to 14 mg once daily if additional glycemic control is needed after at least 30 days on the 7 mg dose. Taking two 7 mg Rybelsus tablets to achieve a 14 mg dose is not recommended. If a dose is missed, the missed dose should be skipped, and the next dose should be taken the following day.

Clinical Results

FDA Approval

The FDA approval of Rybelsus was based on the results from 10 PIONEER clinical trials which included 9,543 adults with type 2 diabetes. The PIONEER trials (PIONEER 1-10) evaluated oral semaglutide versus placebo and versus other type 2 diabetes drugs, including empagliflozin, sitagliptin, liraglutide and dulaglutide. Across the trials, oral semaglutide was shown to reduce A1C and also help patients reduce their body weight. In PIONEER 1 oral semaglutide demonstrated a superior reduction in HbA1c and a superior reduction in body weight at week 26 versus placebo. In PIONEER 1 80% of patients on oral semaglutide 14 mg achieved an HbA1c level below 7% after 26 weeks. In PIONEER 2 oral semaglutide demonstrated a statistically significant reduction in HbA1c and a statistically significant reduction in weight at week 52 versus empagliflozin. In PIONEER 4 oral semaglutide demonstrated a statistically significant reduction in HbA1c and a statistically significant change in body weight at week 52 versus Victoza. The PIONEER 7 trial investigated efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin. In PIONEER 7 around 60% of patients on oral semaglutide achieved an HbA1c level below 7% at week 52 and oral semaglutide demonstrated a superior body weight reduction at week 52 versus sitagliptin. 

Side Effects

Adverse effects associated with the use of Rybelsus may include, but are not limited to, the following:

nausea

abdominal pain

diarrhea

decreased appetite

vomiting

constipation

The Rybelsus drug label comes with the following Black Box Warning: RISK OF THYROID C-CELL TUMORS

  • In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Rybelsus causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
  • Rybelsus is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Rybelsus and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Rybelsus.

Mechanism of Action

Rybelsus (oral semaglutide) is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Additional Information

For additional information regarding Rybelsus oral treatment or type 2 diabetes, please visit the Rybelsus web page.