Rybelsus (semaglutide) in the treatment of obesity

What is Rybelsus? GLP-1 in tablet form

Rybelsus is a prescription medication in tablet form containing the active substance semaglutide. It belongs to the drug class of GLP-1 receptor agonists and works by mimicking the body's own satiety hormone GLP-1 (glucagon-like peptide-1).

Upon food intake, GLP-1 is naturally released from the small intestine and signals to the brain that energy is being supplied to the body. However, the hormone has a very short half-life and is rapidly broken down in the body by the enzyme DPP-4. Semaglutide is structurally modified to resist this breakdown, providing a more long-lasting effect on appetite regulation.

By activating GLP-1 receptors in the brain's appetite center (hypothalamus), semaglutide contributes to reduced hunger and an increased feeling of fullness. Simultaneously, the gastrointestinal tract is also affected through delayed gastric emptying, leading to a more long-lasting satiety after a meal. These effects interact to facilitate a reduced energy intake.

Since peptide-based medications are normally broken down in the gastrointestinal tract, Rybelsus contains an absorption-enhancing excipient, SNAC (sodium N-(8-[2-hydroxybenzoyl]amino)caprylate). This enables semaglutide to be absorbed through the gastric mucosa and reach the blood circulation in active form, making the tablet form possible.

Rybelsus is a medication manufactured by Novo Nordisk Scandinavia AB that is approved for the treatment of type 2 diabetes.

Who can be prescribed Rybelsus for weight loss?

Rybelsus is approved for the treatment of adults with type 2 diabetes and is used as a supplement to diet and physical activity to improve blood sugar control. Rybelsus is not approved for the treatment of obesity, but doctors may in some cases consider so-called off-label use – that is, prescription outside the approved indication – when assessing that the patient is in need of, and may benefit from, the treatment. For such use, the same medical assessment criteria as for medications approved for weight control are usually applied, for example, BMI ≥ 30, or BMI ≥ 27 with at least one weight-related complication (such as high blood pressure, type 2 diabetes, sleep apnea, or elevated blood lipids).

What results can be expected from treatment with oral semaglutide?

In clinical studies, oral semaglutide has shown a significant effect on weight loss in people with overweight and obesity. On average, a weight loss in the range of 10–15 percent of body weight has been observed, depending on dose, treatment duration, and individual factors.

Treatment with oral semaglutide in doses of 50 mg (OASIS-1) in adults with overweight or obesity (without type 2 diabetes) was reported to result in an average weight loss of approximately 15% after 68 weeks, compared to approximately 2.4% in the placebo group.

The observed weight loss is comparable to results from studies of injectable semaglutide, Wegovy (2.4 mg weekly).

It is, however, important to note that these results were achieved in combination with structured lifestyle interventions, including nutritional counseling and regular physical activity. The medication works as a biological support by regulating appetite and energy intake, while lifestyle habits largely determine the long-term outcome of the treatment.

How to take Rybelsus

Rybelsus is taken once daily on an empty stomach, before the first meal of the day. The tablet should be swallowed whole together with a small amount of water (up to approximately 120 ml). After intake, one should wait at least 30 minutes before eating, drinking anything else, or taking other medications.

Correct administration is important for the medication's effect. The absorption of semaglutide through the gastric mucosa is dependent on the absorption-enhancing excipient SNAC and is sensitive to simultaneous food intake or fluid. If the tablet is taken together with food, larger amounts of fluid, or other drinks than plain water (e.g., coffee or juice), absorption may decrease and affect the treatment outcome.

Rybelsus instead of Ozempic or Wegovy – what is the difference?

The primary difference between Rybelsus, Ozempic, and Wegovy is the form of administration. Rybelsus is taken as a daily tablet, while Ozempic and Wegovy are administered as subcutaneous injections once per week. All three medications, however, contain the same active substance, semaglutide.

The differences between the medications mainly concern indication, dosage, and method of administration:

• Wegovy: Given as a weekly injection. It is specifically approved and dose-adapted for the treatment of obesity and overweight with at least one complication.
• Ozempic: Given as a weekly injection. It is approved for the treatment of type 2 diabetes.
• Rybelsus: Taken as a daily tablet and is approved for the treatment of type 2 diabetes.

For patients with a pronounced needle phobia or for those who for practical reasons have difficulties with injection treatment or cold storage, Rybelsus may constitute a more accessible alternative. However, the choice of treatment should always be based on an individual medical assessment.

Common side effects and how to manage them

The most common side effects of treatment with Rybelsus are gastrointestinal and include nausea, diarrhea, constipation, and abdominal pain. These symptoms are a result of the medication's mechanism of action, where gastric emptying is delayed and appetite regulation is affected. The discomfort is usually mild to moderate and generally subsides over time as the body adapts to the treatment.

Gastrointestinal-related symptoms occur mainly at the start of treatment or in connection with dose escalation. Nausea is the most common side effect and can partly be explained by the stomach emptying slower than before.

Through certain measures, side effects can often be reduced:

• Adjust portion sizes: Eat smaller meals and stop the meal at early satiety signals.
• Eat slowly and chew food well: This facilitates digestion and reduces the load on the gastrointestinal tract.
• Avoid high-fat and processed food: Fatty food further delays gastric emptying and can exacerbate nausea and discomfort.
• Ensure adequate fluid intake: This is particularly important to counteract constipation and maintain normal bowel function.

Why strength training and protein are crucial during medical weight loss

To promote a favorable body composition during weight loss, it is important that the treatment is supplemented with sufficient protein intake and regular strength training. The goal is primarily to reduce fat mass while muscle mass is preserved.

Weight loss requires an energy deficit. In an energy deficit, the body uses both fat and muscle tissue as an energy source. Without sufficient stimulus, there is a risk that a larger part of the weight loss will consist of loss of muscle mass.

Regular strength training serves as an important signal to the body to preserve musculature, while a sufficient protein intake provides the building blocks required to maintain muscle tissue. Together, these measures contribute to improving body composition during weight loss.

Preserved muscle mass is also significant from a metabolic perspective, as it has importance for basal energy expenditure. A larger loss of muscle mass can lead to a lowered energy expenditure at rest, which can make it more difficult to maintain the achieved weight over time.

Against this background, it is recommended that protein intake is distributed evenly over the day's meals and that strength training is included regularly, adapted to individual circumstances and ability.

Frequently asked questions about Rybelsus

How much weight do you lose from Rybelsus tablets?

In clinical trials, such as the OASIS-1 study on adults with overweight or obesity (without diabetes), treatment with 50 mg oral semaglutide resulted in an average weight loss of around 15 percent of body weight over 68 weeks. Results vary individually and require changed dietary and exercise habits.

Can you switch from Ozempic (injection) to Rybelsus (tablet)?

Yes, a switch between semaglutide in injection form and tablet form may be possible and in some cases medically motivated, for example, in the case of pronounced needle phobia or when needing to adjust treatment due to side effects or practical reasons.

Such a switch should always take place in close consultation with the treating physician. The dosage strategy needs to be individually adapted, as bioavailability and administration methods differ between the formulation forms. A carefully planned transition is important to ensure maintained treatment effect and good tolerability.

Can I get Rybelsus prescribed if I don't have diabetes?

Rybelsus is formally approved for the treatment of adults with type 2 diabetes. In some cases, doctors may, based on an individual medical assessment, choose to prescribe the medication outside of its approved indication (so-called off-label use).

Such a prescription assumes that the patient has a clear medical need, where factors such as BMI (usually ≥30, or ≥27 with concurrent weight-related comorbidity) and the overall health situation are weighed in. The treatment is given if the expected benefit is judged to exceed the potential risks.

Must one take Rybelsus on an empty stomach to lose weight?

Yes, to ensure optimal absorption, Rybelsus should be taken on an empty stomach with a small amount of water (up to approximately 120 ml). After intake, one should wait at least 30 minutes before eating, drinking anything else, or taking other medications.

What are the most common side effects of Rybelsus?

The most common side effects of treatment with Rybelsus are gastrointestinal and include nausea, diarrhea, vomiting, and constipation. These symptoms occur mainly at the start of treatment or in connection with dose escalation.

The discomfort is generally mild to moderate and tends to subside gradually as the body adapts to the effects of the medication.

Sources

The Lancet. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. 2023. https://pubmed.ncbi.nlm.nih.gov/37385278/

European Medicines Agency (EMA). Rybelsus – EPAR Product Information. https://www.ema.europa.eu/en/medicines/human/EPAR/rybelsus

The New England Journal of Medicine. Once-Weekly Semaglutide in Adults with Overweight or Obesity. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

Journal of Clinical Medicine. Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus. https://pubmed.ncbi.nlm.nih.gov/36614945/