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Rybelsus is an oral prescription medication containing semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist used to improve blood sugar control in adults with type 2 diabetes mellitus. Available in 3 mg, 7 mg, and 14 mg tablet strengths, Rybelsus offers a convenient alternative to injectable diabetes treatments. The formulation includes a specialised absorption enhancer called salcaprozate sodium (SNAC), which enables semaglutide to be absorbed through the stomach lining. This article explains the active and inactive ingredients in Rybelsus, how they work together, and important safety considerations for patients prescribed this medication.
Quick Answer: Rybelsus contains semaglutide as the active ingredient (3 mg, 7 mg, or 14 mg per tablet) plus inactive ingredients including salcaprozate sodium (SNAC), which enables oral absorption.
Rybelsus is an oral prescription medication used to improve blood sugar control in adults with type 2 diabetes mellitus. It contains semaglutide and is a glucagon-like peptide-1 (GLP-1) receptor agonist available in tablet form, offering an alternative to injectable diabetes treatments. Rybelsus is typically prescribed alongside diet and exercise modifications when other diabetes medications have not provided adequate glycaemic control.
The medication works by mimicking the action of a naturally occurring hormone called GLP-1, which plays a crucial role in regulating blood glucose levels. When you eat, GLP-1 is released in the intestines and signals the pancreas to produce insulin in response to elevated blood sugar. Rybelsus enhances this natural process by binding to GLP-1 receptors, thereby stimulating insulin secretion only when blood glucose levels are raised. This glucose-dependent mechanism reduces the risk of hypoglycaemia compared to some other diabetes medications, although the risk increases when used with insulin or sulfonylureas (which may require dose reduction of these medicines).
Additionally, Rybelsus slows gastric emptying, which means food moves more slowly from the stomach into the small intestine. This helps to reduce post-meal blood sugar spikes and can promote a feeling of fullness, potentially supporting weight management. The medication also suppresses glucagon secretion—a hormone that raises blood glucose—further contributing to improved glycaemic control.
Rybelsus is available in three strengths: 3 mg, 7 mg, and 14 mg tablets. Treatment begins with the 3 mg dose for 30 days as an initiation dose to help the body adjust (this dose is not effective for glycaemic control), before increasing to 7 mg. If additional glycaemic control is needed after at least 30 days on 7 mg, the dose may be increased to 14 mg.
Rybelsus must be taken correctly to ensure absorption: take on an empty stomach with up to 120 ml of water, swallow the tablet whole, and wait at least 30 minutes before eating, drinking, or taking other oral medicines. If a dose is missed, skip that dose and take the next dose the following day.
The MHRA has approved Rybelsus for use within the UK, and NICE guidance (NG28) supports its use in specific clinical scenarios for type 2 diabetes management.
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The active pharmaceutical ingredient in Rybelsus is semaglutide, a synthetic analogue of human GLP-1 with 94% structural similarity to the natural hormone. Semaglutide has been modified to resist breakdown by the enzyme dipeptidyl peptidase-4 (DPP-4), which normally degrades natural GLP-1 within minutes. This modification extends semaglutide's half-life to approximately one week, although the once-daily oral dosing primarily reflects the formulation's bioavailability characteristics rather than the half-life.
Each Rybelsus tablet contains a precise amount of semaglutide as the active ingredient:
3 mg tablet: contains 3 mg of semaglutide
7 mg tablet: contains 7 mg of semaglutide
14 mg tablet: contains 14 mg of semaglutide
Semaglutide belongs to the GLP-1 receptor agonist class of antidiabetic medications. It works by selectively binding to and activating GLP-1 receptors found in pancreatic beta cells, the gastrointestinal tract, and certain areas of the brain involved in appetite regulation. Through this mechanism, semaglutide enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon levels, and slows gastric emptying.
The oral bioavailability of semaglutide is naturally very low due to enzymatic degradation in the stomach and poor absorption across the intestinal wall. To overcome this challenge, Rybelsus tablets incorporate a specialised absorption enhancer (discussed in the next section) that facilitates semaglutide absorption in the stomach. This innovative formulation technology enables therapeutic levels of semaglutide to reach the bloodstream when taken correctly—specifically on an empty stomach with no more than 120 ml of water, swallowing the tablet whole, and waiting at least 30 minutes before eating, drinking, or taking other medications.
Clinical trials have demonstrated that semaglutide significantly reduces HbA1c levels and body weight in people with type 2 diabetes. The cardiovascular outcomes trial for oral semaglutide (PIONEER-6) showed non-inferiority for major adverse cardiovascular events compared to placebo in patients with type 2 diabetes at high cardiovascular risk.
In addition to the active ingredient semaglutide, Rybelsus tablets contain several inactive ingredients (excipients) that are essential for the tablet's formulation, stability, and—most importantly—for enabling oral absorption of semaglutide. These excipients do not have therapeutic effects themselves but serve critical pharmaceutical functions.
The key inactive ingredient in Rybelsus is salcaprozate sodium (SNAC), a novel absorption enhancer that makes oral delivery of semaglutide possible. SNAC temporarily and locally increases the pH in the stomach, which protects semaglutide from enzymatic degradation. It also enhances the permeability of the gastric mucosa, facilitating semaglutide absorption directly through the stomach lining into the bloodstream. Without SNAC, semaglutide would be broken down before it could be absorbed, rendering oral administration ineffective.
According to the UK Summary of Product Characteristics (SmPC), other inactive ingredients in Rybelsus tablets include:
Microcrystalline cellulose: a bulking agent that provides structure to the tablet
Povidone K90: a binding agent that holds the tablet ingredients together
Magnesium stearate: a lubricant that prevents ingredients from sticking to manufacturing equipment
The tablet coating contains:
Polyvinyl alcohol (partially hydrolysed): a film-forming polymer
Titanium dioxide (E171): a white pigment that gives the tablet its appearance
Macrogol 3350: a plasticiser that provides flexibility to the coating
Talc: an anti-sticking agent
Iron oxide red (E172) (in 7 mg and 14 mg tablets only)
Rybelsus is considered essentially sodium-free, containing less than 1 mmol sodium (23 mg) per tablet.
These excipients are carefully selected and tested to ensure they meet pharmaceutical quality standards and do not interfere with semaglutide's therapeutic action. The specific combination and ratio of these ingredients are crucial for maintaining the tablet's stability during storage and ensuring consistent drug release and absorption when taken as directed. All excipients used in Rybelsus are approved by the MHRA and EMA for use in oral pharmaceutical products.
Based on the excipient list in the UK SmPC, Rybelsus does not contain common food allergens such as gluten, lactose, soya, or nuts. However, as with any medication, it is important to review the complete ingredient list with your healthcare provider if you have known allergies or sensitivities to pharmaceutical excipients.
The inactive ingredients in Rybelsus are generally well-tolerated, but some individuals may have sensitivities to specific excipients. For example, macrogol (polyethylene glycol) compounds, whilst rare, can cause allergic reactions in susceptible individuals. If you have previously experienced allergic reactions to medications containing macrogol or polyvinyl alcohol, inform your doctor before starting Rybelsus.
Contraindications and important safety considerations include:
Hypersensitivity: Do not take Rybelsus if you have had a serious allergic reaction to semaglutide or any of the tablet ingredients.
Type 1 diabetes or diabetic ketoacidosis: Rybelsus is not appropriate for these conditions.
Pregnancy and breastfeeding: Rybelsus is not recommended during pregnancy or breastfeeding. Women of childbearing potential should use contraception and discontinue Rybelsus at least 2 months before a planned pregnancy.
Age restrictions: Not indicated for use in patients under 18 years of age.
Important safety warnings include:
Diabetic retinopathy: Rapid improvements in glucose control have been associated with temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored closely.
Gallbladder disease: GLP-1 receptor agonists have been associated with gallbladder events, including cholelithiasis and cholecystitis.
Dehydration: Due to gastrointestinal effects, dehydration may occur, potentially leading to acute kidney injury. Take precautions to maintain fluid intake.
Hypoglycaemia risk: When used with insulin or sulfonylureas, the risk of hypoglycaemia increases; dose reduction of these medications may be required.
Common adverse effects related to Rybelsus ingredients and mechanism of action include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain, and constipation. These effects are usually mild to moderate and tend to diminish over time as the body adjusts to the medication. Starting with the lower 3 mg dose helps minimise these symptoms.
If you experience signs of a severe allergic reaction—such as swelling of the face, lips, tongue, or throat, difficulty breathing, or severe rash—seek immediate medical attention. Contact your GP if you develop persistent severe abdominal pain, as this may indicate pancreatitis, a rare but serious adverse effect. Always inform your healthcare team about all medications and supplements you are taking, as Rybelsus may interact with other drugs, particularly those that need to be absorbed quickly or require specific timing relative to meals. Increased exposure to levothyroxine may occur; thyroid function should be monitored. If taking warfarin or other coumarins, INR monitoring is advised.
Suspected adverse reactions should be reported via the Yellow Card Scheme at yellowcard.mhra.gov.uk.
The active ingredient in Rybelsus is semaglutide, a GLP-1 receptor agonist available in 3 mg, 7 mg, or 14 mg tablet strengths. Semaglutide works by enhancing insulin secretion, suppressing glucagon, and slowing gastric emptying to improve blood sugar control in type 2 diabetes.
No, Rybelsus does not contain common food allergens such as gluten, lactose, soya, or nuts. However, patients with known sensitivities to pharmaceutical excipients like macrogol should discuss the complete ingredient list with their healthcare provider.
SNAC (salcaprozate sodium) is an absorption enhancer that enables oral delivery of semaglutide. It temporarily increases stomach pH to protect semaglutide from degradation and enhances permeability of the gastric mucosa, allowing the medication to be absorbed into the bloodstream.
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