What is the use of Rybelsus (semaglutide)?

From the Guidelines

Rybelsus (semaglutide) is recommended as a treatment option for type 2 diabetes due to its proven efficacy in reducing the risk of major adverse cardiovascular events, as demonstrated in the PIONEER 6 trial 1. When prescribing Rybelsus, it is essential to consider the patient's individual needs and medical history. The medication is taken once daily, typically starting at 3 mg for 30 days, then increasing to 7 mg, with a possible increase to 14 mg if needed for better blood sugar control. Key points to consider when prescribing Rybelsus include:

• The medication must be taken on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before eating, drinking, or taking other oral medications, as food interferes with absorption 1.
• Common side effects include nausea, vomiting, diarrhea, abdominal pain, and decreased appetite, which often improve over time.
• Rybelsus works by stimulating insulin release when blood sugar is high, slowing stomach emptying, and reducing appetite, leading to improved blood sugar control and often modest weight loss.
• It is not recommended for people with type 1 diabetes, diabetic ketoacidosis, personal or family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. The PIONEER 6 trial demonstrated that oral semaglutide was noninferior to placebo for the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.79; 95% CI 0.57–1.11; P < 0.001) 1. Overall, Rybelsus is a valuable treatment option for patients with type 2 diabetes, offering benefits in terms of cardiovascular risk reduction and glycemic control.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Overview of Rybelsus

• Rybelsus, also known as oral semaglutide, is a glucagon-like peptide-1 (GLP-1) receptor agonist with 94% homology to human GLP-1 2, 3.
• It is the first GLP-1RA developed for oral administration and is indicated for use as an add-on combination therapy or as a monotherapy for type 2 diabetes 2.
• Oral semaglutide has been shown to be effective in achieving glycemic control, reducing body weight, and decreasing systolic blood pressure 2, 4.

Mechanism of Action and Pharmacokinetics

• Oral semaglutide works by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 4.
• It has a high affinity for the fatty acid binding site of albumin, which extends its half-life by protecting it from degradation by DPP-4 3.
• The co-formulation of semaglutide with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl]amino) caprylate (SNAC) enables its oral administration 2, 3.

Clinical Efficacy and Safety

• Oral semaglutide has been shown to be well-tolerated, with a safety profile consistent with the GLP-1RA drug class 2, 5.
• The most common adverse events are gastrointestinal, with nausea and diarrhea being the most frequently reported manifestations 2, 6.
• Cardiovascular safety has been established, with a significantly lower risk of major adverse cardiovascular events compared to placebo in high-risk type 2 diabetes patients 6.

Potential Benefits and Limitations

• Oral semaglutide may be an attractive option for patients with type 2 diabetes who require improved glycemic control, would like to lose weight, and are not interested in injectable therapy 5.
• However, the lack of positive cardiovascular and renal data was initially a limitation to its use, but recent studies have addressed these concerns 5, 6.
• Oral semaglutide has been shown to be of continuous benefit in patients with type 2 diabetes at various stages, and may enable earlier improvement in glycemic control 3.