Rybelsus (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for treating type 2 diabetes mellitus in adults. As the first oral GLP-1 receptor agonist available, it offers an alternative to injectable formulations. Rybelsus works by mimicking natural GLP-1, enhancing glucose-dependent insulin secretion, suppressing glucagon release, and slowing gastric emptying to improve blood glucose control. This once-daily tablet is prescribed as monotherapy or in combination with other diabetes medications when diet, exercise, and existing treatments do not achieve target HbA1c levels. Understanding how Rybelsus functions as a GLP-1 receptor agonist helps patients and clinicians make informed treatment decisions.
Quick Answer: Yes, Rybelsus is a glucagon-like peptide-1 (GLP-1) receptor agonist containing semaglutide, the first oral formulation in this drug class.
Rybelsus (semaglutide) is an oral medication licensed in the UK for the treatment of type 2 diabetes mellitus in adults. It is manufactured by Novo Nordisk and represents the first glucagon-like peptide-1 (GLP-1) receptor agonist available in tablet form, offering an alternative to injectable formulations of the same drug class.
The active ingredient, semaglutide, works by mimicking the action of naturally occurring GLP-1, a hormone released by the intestine in response to food intake. Semaglutide binds to and activates GLP-1 receptors found predominantly in pancreatic beta cells, the brain, and the gastrointestinal tract. This activation triggers several physiological responses that help regulate blood glucose levels.
Specifically, Rybelsus enhances glucose-dependent insulin secretion from pancreatic beta cells, meaning insulin is released only when blood glucose levels are elevated. This mechanism reduces the risk of hypoglycaemia compared to some other diabetes medications. Additionally, semaglutide suppresses glucagon secretion from pancreatic alpha cells, which further prevents excessive glucose production by the liver.
Beyond glycaemic control, Rybelsus also slows gastric emptying, prolonging the time food remains in the stomach. This contributes to increased satiety and reduced appetite, which may support weight management—a beneficial effect for many individuals with type 2 diabetes, though the medication is not licensed for weight loss. The medication is typically taken once daily on an empty stomach, at least 30 minutes before the first food, drink, or other oral medications of the day, to ensure optimal absorption.
Rybelsus treatment begins with a 3 mg once-daily dose for 30 days, then increases to 7 mg once daily. If additional glycaemic control is needed after at least 30 days, the dose may be increased to 14 mg once daily. Tablets should be swallowed whole with up to 120 mL of water; they should not be split, crushed or chewed.
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Start HereRybelsus is indicated for adults aged 18 years and over with type 2 diabetes mellitus to improve glycaemic control. According to the Medicines and Healthcare products Regulatory Agency (MHRA) and National Institute for Health and Care Excellence (NICE) guidance, it may be prescribed as:
Monotherapy when diet and exercise alone do not provide adequate glycaemic control and when metformin is considered inappropriate due to intolerance or contraindications
Add-on therapy in combination with other glucose-lowering medications, including metformin, sulfonylureas, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or insulin, when existing treatment does not achieve target HbA1c levels
NICE Technology Appraisal 653 (TA653) recommends oral semaglutide as an option for treating type 2 diabetes in adults when a GLP-1 receptor agonist would otherwise be appropriate according to NICE guideline NG28. This includes considering GLP-1 receptor agonists like Rybelsus for people with type 2 diabetes who have a body mass index (BMI) of 35 kg/m² or higher (or 32.5 kg/m² or higher for those of South Asian or Chinese descent) and who would benefit from weight loss, or when insulin therapy would have significant occupational implications or weight gain would cause significant clinical or psychological problems.
Rybelsus is not suitable for everyone. The UK Summary of Product Characteristics (SmPC) lists hypersensitivity to semaglutide or any of the excipients as a contraindication. It should not be used in people with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Caution is advised in patients with severe gastrointestinal disease, a history of pancreatitis, or severe renal impairment. While no dose adjustment is required in renal impairment, patients should be monitored due to potential dehydration risk from gastrointestinal side effects. When initiating Rybelsus in patients already taking sulfonylureas or insulin, a reduction in the dose of these medications should be considered to reduce the risk of hypoglycaemia.
Women who are pregnant, planning pregnancy, or breastfeeding should discuss alternative treatments with their healthcare provider. Semaglutide is not recommended during pregnancy and should be discontinued at least 2 months before a planned pregnancy. It is also not recommended during breastfeeding.
Like all medications, Rybelsus can cause side effects, although not everyone will experience them. The most frequently reported adverse effects are gastrointestinal in nature and typically occur during the initial weeks of treatment or following dose escalation.
Very common side effects (affecting more than 1 in 10 people) include:
Nausea – often the most prominent symptom, usually diminishing over time
Diarrhoea – may be transient but can occasionally persist
Common side effects (affecting up to 1 in 10 people) include:
Vomiting
Abdominal pain or discomfort
Decreased appetite
These gastrointestinal symptoms are generally mild to moderate in severity and tend to improve as the body adjusts to the medication. Taking Rybelsus exactly as prescribed—on an empty stomach with no more than 120 mL of water—can help optimise tolerability.
Hypoglycaemia (low blood sugar) is a common side effect, particularly when Rybelsus is used in combination with sulfonylureas or insulin. Patients should be educated about recognising symptoms such as tremor, sweating, confusion, palpitations, and hunger, and advised to carry a source of fast-acting carbohydrate. When starting Rybelsus, insulin doses should not be abruptly stopped or rapidly reduced due to the risk of diabetic ketoacidosis.
Important safety considerations include:
Diabetic retinopathy complications: Patients with pre-existing diabetic retinopathy should be monitored closely, particularly during rapid improvement in glucose control
Gallbladder disease: Semaglutide has been associated with an increased risk of cholelithiasis and cholecystitis
Acute pancreatitis: Patients should seek immediate medical attention if they experience severe, persistent abdominal pain that may radiate to the back, often accompanied by vomiting
Dehydration and acute kidney injury: The gastrointestinal effects may lead to dehydration, which can cause acute kidney injury; maintaining adequate fluid intake is important
Rybelsus may affect the absorption of other oral medications due to its effects on gastric emptying. Levothyroxine exposure may be increased; thyroid function should be monitored in patients taking both medications. For patients on warfarin or other coumarins, INR monitoring is advised when starting or stopping Rybelsus.
Patients should contact their GP or diabetes specialist nurse if:
Gastrointestinal side effects persist beyond the first few weeks or significantly impact quality of life
They experience signs of dehydration due to vomiting or diarrhoea
They have recurrent hypoglycaemia
They develop visual changes or symptoms of gallbladder disease (e.g., right upper abdominal pain)
Any new or concerning symptoms develop
Regular monitoring of HbA1c, renal function, and body weight is recommended during treatment with Rybelsus. Patients are encouraged to report suspected side effects to the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).
Yes, Rybelsus is definitively a GLP-1 receptor agonist. It belongs to the pharmacological class of medications known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which are designed to mimic the action of the endogenous incretin hormone GLP-1.
The active pharmaceutical ingredient in Rybelsus is semaglutide, a GLP-1 analogue with 94% structural homology to human GLP-1. Semaglutide has been modified to resist degradation by the enzyme dipeptidyl peptidase-4 (DPP-4), which normally breaks down natural GLP-1 within minutes. This modification, combined with albumin binding, extends semaglutide's half-life to approximately one week.
What distinguishes Rybelsus from other GLP-1 receptor agonists such as Ozempic (injectable semaglutide), Victoza (liraglutide), Trulicity (dulaglutide), and Byetta (exenatide) is its oral formulation. Historically, GLP-1 RAs have been administered via subcutaneous injection because peptide-based drugs are typically degraded in the gastrointestinal tract. Rybelsus overcomes this challenge through co-formulation with an absorption enhancer called sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), which facilitates absorption of semaglutide across the gastric mucosa.
The combination of semaglutide's long half-life and the SNAC-enabled gastric absorption underpin the efficacy of Rybelsus. The once-daily dosing regimen is determined by oral absorption characteristics and exposure requirements for optimal glycaemic control.
The classification of Rybelsus as a GLP-1 receptor agonist is reflected in its Summary of Product Characteristics (SmPC) approved by the Medicines and Healthcare products Regulatory Agency (MHRA) and available on the electronic medicines compendium (emc). This classification is clinically significant because it informs prescribing decisions, helps predict the side effect profile, and guides patient counselling regarding mechanism of action and expected therapeutic outcomes.
For patients seeking clarification, Rybelsus contains the same active drug (semaglutide) as Ozempic and Wegovy, but formulated for oral administration. All three are GLP-1 receptor agonists with similar mechanisms of action, differing primarily in route of administration and licensed indications. While Rybelsus and Ozempic are licensed for treatment of type 2 diabetes, Wegovy (semaglutide 2.4 mg) is specifically licensed for weight management in the UK.
Rybelsus is the first oral GLP-1 receptor agonist, whereas other GLP-1 medications such as Ozempic, Victoza, and Trulicity are administered by subcutaneous injection. It contains the same active ingredient (semaglutide) as Ozempic but uses an absorption enhancer to enable oral administration.
Rybelsus is licensed in the UK only for treating type 2 diabetes mellitus, not for weight loss. Wegovy (semaglutide 2.4 mg) is the formulation specifically licensed for weight management in the UK.
Nausea is a very common side effect that typically improves over time. If gastrointestinal symptoms persist beyond the first few weeks or significantly impact your quality of life, contact your GP or diabetes specialist nurse for advice on managing symptoms or adjusting treatment.
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