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Rybelsus (semaglutide) is an oral GLP-1 receptor agonist licensed in the UK for type 2 diabetes mellitus. Diarrhoea is a very common side effect of Rybelsus, affecting at least 1 in 10 patients according to UK product information. This occurs because GLP-1 receptors throughout the gastrointestinal tract influence gut motility and secretions when activated. Whilst not everyone experiences this adverse effect, understanding its frequency, typical duration, and management strategies is essential for patients and healthcare professionals. Most cases are mild to moderate, occurring early in treatment, and often improve as the body adjusts to the medication.
Quick Answer: Rybelsus (semaglutide) very commonly causes diarrhoea, affecting at least 1 in 10 patients, due to GLP-1 receptor activation throughout the gastrointestinal tract.
Rybelsus (semaglutide) is an oral glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for the treatment of type 2 diabetes mellitus. Like other medications in its class, Rybelsus can indeed cause diarrhoea as a recognised adverse effect. According to the UK Summary of Product Characteristics (SmPC), diarrhoea is classified as a very common side effect, occurring in at least 1 in 10 patients.
The mechanism behind this side effect relates to how semaglutide works. GLP-1 receptors are present throughout the gastrointestinal tract, and when activated by Rybelsus, they can alter both gut motility and secretions. While the medication slows gastric emptying (the rate at which the stomach releases contents into the small intestine), its effects on intestinal function can lead to various digestive symptoms, including diarrhoea, nausea, vomiting, and abdominal discomfort.
It is important to note that not everyone taking Rybelsus will experience diarrhoea. Individual responses to medication vary considerably, and whilst some patients may develop troublesome gastrointestinal symptoms, others tolerate the treatment well with minimal or no digestive upset. The Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have documented diarrhoea as a known adverse reaction in the product information for Rybelsus.
For patients prescribed Rybelsus, understanding that diarrhoea is a potential side effect—rather than an unexpected complication—can help with treatment adherence and appropriate management strategies. Healthcare professionals typically discuss these possibilities before initiating therapy to ensure patients are well-informed about what to expect.
Clinical trial data provides valuable insight into the frequency of diarrhoea associated with Rybelsus. In pivotal registration studies, diarrhoea was reported as a very common adverse reaction (affecting ≥1/10 patients), with an incidence of approximately 10-15% in patients taking the 14 mg dose and slightly lower but still around 10% in those taking the 7 mg dose, according to the European Medicines Agency's European Public Assessment Report (EPAR).
The incidence of diarrhoea appears to be dose-dependent to some extent. Patients taking the 14 mg maintenance dose typically experience higher rates of gastrointestinal adverse effects compared to those on the 7 mg dose. The gradual dose escalation protocol recommended for Rybelsus—starting at 3 mg daily for one month (a non-therapeutic starter dose for tolerability), then increasing to 7 mg, and potentially to 14 mg after a further month if needed and tolerated—is specifically designed to improve gastrointestinal tolerability and reduce the severity of these side effects.
Most cases of diarrhoea associated with Rybelsus are mild to moderate in severity and tend to occur during the initial weeks of treatment or following dose increases. For many patients, these symptoms improve or resolve completely as the body adjusts to the medication, typically within the first few weeks to months of therapy. Persistent or severe diarrhoea is less common but does occur in a small subset of patients.
Post-marketing surveillance generally aligns with trial data, confirming that whilst diarrhoea is a recognised and relatively common side effect, it does not affect all patients. Healthcare professionals should counsel patients that gastrointestinal symptoms, if they occur, are usually temporary and manageable with appropriate supportive measures.
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Effective management of diarrhoea whilst taking Rybelsus involves both non-pharmacological and pharmacological strategies. The first-line approach typically focuses on dietary modifications and lifestyle adjustments. Patients experiencing diarrhoea should ensure adequate fluid intake to prevent dehydration, which is particularly important for individuals with diabetes who may already be at increased risk of fluid imbalance. Oral rehydration solutions can be beneficial if diarrhoea is frequent or prolonged.
Dietary adjustments can significantly help manage symptoms. Patients may benefit from:
Avoiding high-fat, spicy, or heavily processed foods that can exacerbate gastrointestinal upset
Limiting caffeine and alcohol, both of which can stimulate bowel movements
Eating smaller, more frequent meals rather than large portions
Temporarily reducing dietary fibre intake if diarrhoea is severe
Identifying and avoiding any specific food triggers
It is crucial that patients continue taking Rybelsus as prescribed unless advised otherwise by their healthcare provider. The medication should be taken on an empty stomach with no more than 120 ml of water, at least 30 minutes before the first food, drink, or other oral medications of the day. The tablet should be swallowed whole and not split, crushed or chewed. Altering the administration schedule or stopping treatment without medical guidance can affect glycaemic control.
Over-the-counter antidiarrhoeal medications such as loperamide may be considered for symptomatic relief, but patients should consult their GP or pharmacist before using these products, particularly if diarrhoea is persistent or accompanied by other concerning symptoms. Antidiarrhoeal medications should be avoided if there is blood in the stool or fever. In some cases, healthcare professionals may consider temporarily reducing the Rybelsus dose or implementing a slower titration schedule to improve tolerability.
Patients should maintain regular contact with their diabetes care team, particularly during the first few months of treatment. Monitoring blood glucose levels remains important, as gastrointestinal symptoms and changes in food intake can affect glycaemic control. Those taking sulfonylureas or insulin may need dose adjustments to prevent hypoglycaemia if food intake is reduced. Additionally, patients taking levothyroxine should be aware that Rybelsus may affect its absorption; these medications should be taken at least 30 minutes apart, and thyroid function tests may be needed.
Patients should be vigilant for signs of dehydration (passing little urine, dizziness, confusion), particularly if they are older or taking medications such as diuretics, ACE inhibitors or NSAIDs, as there is a risk of acute kidney injury. If diarrhoea is significantly impacting quality of life or treatment adherence, alternative glucose-lowering therapies may need to be discussed.
Suspected adverse reactions to Rybelsus should be reported via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or the Yellow Card app).
Whilst mild diarrhoea is a recognised side effect of Rybelsus that often improves with time, certain symptoms warrant prompt medical attention. Patients should contact their GP or diabetes specialist nurse if diarrhoea is severe, persistent (lasting more than a few days), or significantly affecting their daily activities and quality of life. Medical review is particularly important if symptoms are worsening rather than improving over time.
Red flag symptoms that require urgent medical assessment include:
Blood in the stool or black, tarry stools
Severe or persistent abdominal pain (especially if radiating to the back, which may indicate pancreatitis)
Signs of dehydration (excessive thirst, dark urine, dizziness, confusion, passing little urine)
Fever accompanying diarrhoea
Persistent vomiting preventing adequate fluid intake
Rapid or unintended weight loss beyond the expected therapeutic effect
Symptoms of hypoglycaemia (low blood sugar) that are difficult to manage
Abdominal pain with fever or yellowing of the skin/eyes (possible gallbladder disease)
Patients should also seek medical advice if they are unable to maintain adequate nutrition or hydration due to gastrointestinal symptoms, or if they need to take other medications but cannot tolerate them due to digestive upset. This is particularly relevant for individuals taking multiple medications for diabetes or other chronic conditions.
For urgent concerns outside of GP hours, patients should contact NHS 111 for advice. For severe symptoms such as significant dehydration, fainting, severe persistent abdominal pain, or bloody stools, patients should attend A&E or call 999.
NICE guidance on type 2 diabetes management (NG28) emphasises the importance of individualised treatment approaches and regular medication review. If gastrointestinal side effects are intolerable despite supportive measures, healthcare professionals should reassess the treatment plan. Alternative GLP-1 receptor agonists, SGLT2 inhibitors, or other glucose-lowering therapies may be more suitable for some patients.
It is important that patients do not discontinue Rybelsus abruptly without medical guidance, as this can lead to deterioration in glycaemic control. Any decision to modify or stop treatment should be made collaboratively with the diabetes care team, taking into account the balance between therapeutic benefits and adverse effects. Regular follow-up appointments allow for ongoing assessment of treatment tolerability and effectiveness, ensuring optimal diabetes management whilst minimising the impact of side effects on patient wellbeing.
Diarrhoea associated with Rybelsus is usually mild to moderate and occurs during the initial weeks of treatment or following dose increases. For most patients, symptoms improve or resolve completely within the first few weeks to months as the body adjusts to the medication.
Over-the-counter antidiarrhoeal medications such as loperamide may be considered for symptomatic relief, but patients should consult their GP or pharmacist before use. Antidiarrhoeal medications should be avoided if there is blood in the stool or fever present.
Contact your GP if diarrhoea is severe, persistent (lasting more than a few days), or significantly affecting daily life. Seek urgent medical attention for red flag symptoms including blood in stools, severe abdominal pain, signs of dehydration, fever, or persistent vomiting.
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