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Does Rybelsus cause blood clots? This is a common concern amongst patients prescribed this oral medication for type 2 diabetes. Rybelsus (semaglutide) is a GLP-1 receptor agonist licensed in the UK to improve glycaemic control. Current clinical evidence and regulatory data from the MHRA, EMA, and extensive PIONEER trials show no established direct link between Rybelsus and increased risk of blood clots. Whilst people with type 2 diabetes do face elevated thrombotic risk, this stems from the metabolic condition itself rather than Rybelsus. Understanding the evidence helps patients and clinicians make informed treatment decisions based on comprehensive cardiovascular risk assessment.
Quick Answer: Rybelsus (semaglutide) is not associated with an increased risk of blood clots based on current clinical evidence and UK regulatory data.
Rybelsus (semaglutide) is an oral GLP-1 receptor agonist licensed in the UK for the treatment of type 2 diabetes mellitus. Many patients and healthcare professionals have questioned whether this medication increases the risk of blood clots (venous thromboembolism or arterial thrombosis). Based on current clinical evidence and regulatory data, there is no established direct link between Rybelsus and an increased risk of blood clots.
The extensive clinical trial programme for semaglutide, including the PIONEER studies that led to Rybelsus approval, did not identify blood clots as a significant adverse effect. The UK Summary of Product Characteristics (SmPC) for Rybelsus does not list thromboembolism as a known side effect. The European Medicines Agency (EMA) European Public Assessment Report (EPAR) for Rybelsus similarly does not highlight thrombotic events as a safety concern.
Mechanism of action considerations further support this safety profile. Semaglutide works by mimicking the incretin hormone GLP-1, which stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon release, and slows gastric emptying. This pharmacological mechanism does not directly affect coagulation pathways or platelet function in ways that would promote thrombosis.
However, it is important to recognise that people with type 2 diabetes have an inherently elevated risk of cardiovascular events, including blood clots, due to the metabolic condition itself rather than the medication used to treat it. Any concerns about clotting should be evaluated in the broader context of individual cardiovascular risk factors, comorbidities, and the overall benefit-risk profile of diabetes management. Patients should discuss any specific concerns with their GP or diabetes specialist team.
If you experience any side effects while taking Rybelsus, you can report them directly to the MHRA through the Yellow Card Scheme at yellowcard.mhra.gov.uk.
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Individuals with type 2 diabetes face an approximately 1.3 to 2 times increased risk of venous thromboembolism (VTE) compared to the general population, independent of medication use. This elevated risk stems from multiple interconnected metabolic and vascular abnormalities characteristic of the condition.
Key risk factors include:
Hyperglycaemia and insulin resistance – Chronic elevated blood glucose levels promote endothelial dysfunction, increase platelet reactivity, and enhance coagulation factor activity, creating a prothrombotic state
Obesity and metabolic syndrome – Excess adipose tissue, particularly visceral fat, produces inflammatory cytokines that activate coagulation pathways and impair fibrinolysis
Dyslipidaemia – Abnormal lipid profiles common in diabetes contribute to atherosclerosis and arterial thrombosis
Hypertension – Elevated blood pressure damages blood vessel walls and promotes clot formation
Chronic inflammation – Low-grade systemic inflammation in diabetes increases levels of fibrinogen and other clotting factors
Additional considerations that compound thrombotic risk include reduced mobility (particularly in those with diabetic complications), smoking, advancing age, and presence of diabetic kidney disease. Women with diabetes taking combined hormonal contraception face further elevated VTE risk, while those using hormone replacement therapy should note that transdermal formulations generally carry lower thrombotic risk than oral preparations.
NICE guidance (NG28) emphasises the importance of comprehensive cardiovascular risk assessment in all people with type 2 diabetes. This includes regular monitoring of HbA1c, blood pressure, lipid profiles, and renal function. Optimising these parameters through lifestyle modification and appropriate pharmacotherapy helps reduce overall cardiovascular risk. The focus should remain on treating the underlying metabolic disorder to mitigate these inherent dangers.
Whilst Rybelsus itself is not associated with increased clotting risk, patients with type 2 diabetes should remain vigilant for signs and symptoms of thromboembolism due to their underlying condition. Early recognition and prompt medical attention are crucial for optimal outcomes.
Deep vein thrombosis (DVT) typically presents with:
Swelling in one leg (rarely both)
Pain or tenderness, often starting in the calf
Warmth and redness over the affected area
Visible surface veins
Leg feeling heavy or aching
Pulmonary embolism (PE), which occurs when a clot travels to the lungs, may cause:
Sudden shortness of breath or difficulty breathing
Sharp chest pain that worsens with deep breathing or coughing
Rapid heart rate or palpitations
Coughing up blood
Feeling lightheaded or fainting
Arterial thrombosis affecting coronary or cerebral circulation presents as:
Chest pain, pressure, or discomfort (potential myocardial infarction)
Sudden weakness or numbness, particularly on one side of the body
Difficulty speaking or understanding speech
Vision changes or loss
Severe headache with no known cause
It is important to note that these symptoms can occur in anyone with diabetes, regardless of which glucose-lowering medication they take. They are not specific side effects of Rybelsus. However, because diabetes itself increases thrombotic risk, maintaining awareness of these warning signs is an essential component of self-management.
Patients should not discontinue Rybelsus if they experience these symptoms without medical guidance, as the medication plays an important role in glycaemic control. Instead, immediate medical assessment is required to determine the cause and appropriate treatment. The NHS and NICE (NG158) have established pathways for the assessment of suspected DVT or PE, which may include clinical probability scoring, D-dimer testing and appropriate imaging.
Understanding when to contact healthcare services is vital for patient safety. Immediate emergency care (999 or A&E attendance) is warranted if you experience:
Sudden severe chest pain or pressure
Difficulty breathing or severe shortness of breath
Signs of stroke (facial drooping, arm weakness, speech difficulty)
Coughing up blood
Sudden collapse or loss of consciousness
These symptoms require urgent evaluation regardless of medication use, as they may indicate life-threatening conditions requiring immediate intervention.
Contact your GP or diabetes specialist nurse within 24 hours if you notice:
New or worsening leg swelling, pain, or discolouration
Unexplained persistent breathlessness during normal activities
Unusual bruising or bleeding
Concerns about your overall cardiovascular risk
If you're unsure about the urgency of your symptoms, NHS 111 can provide guidance on appropriate next steps.
Routine medication reviews provide an opportunity to discuss any concerns about Rybelsus and thrombotic risk. Your healthcare team can:
Assess your individual cardiovascular risk profile using validated tools
Review all medications that might influence clotting risk
Ensure appropriate thromboprophylaxis if you require hospitalisation or surgery
Optimise management of diabetes and associated cardiovascular risk factors
Provide reassurance based on current evidence
If you have specific risk factors for blood clots—such as previous VTE, thrombophilia, recent surgery, prolonged immobility, or active cancer—inform your prescriber before starting Rybelsus. Importantly, Rybelsus should not be used during pregnancy, and women should discuss with their healthcare provider if pregnancy is planned or occurs while taking this medication.
Patients should never stop taking Rybelsus due to unfounded concerns about blood clots without consulting their healthcare team. Uncontrolled diabetes poses far greater cardiovascular risks than the medication used to treat it. Open communication with your diabetes care team ensures that treatment decisions are based on evidence, individual circumstances, and comprehensive risk-benefit assessment aligned with NICE guidance for type 2 diabetes management.
No, blood clotting is not listed as a known side effect of Rybelsus in the UK Summary of Product Characteristics. Extensive clinical trials have not identified thromboembolism as a significant adverse effect of semaglutide.
People with type 2 diabetes face approximately 1.3 to 2 times increased risk of venous thromboembolism due to metabolic abnormalities including hyperglycaemia, insulin resistance, chronic inflammation, and endothelial dysfunction. These factors create a prothrombotic state independent of diabetes medications.
Seek immediate emergency care (999 or A&E) for sudden severe chest pain, difficulty breathing, signs of stroke, or coughing up blood. Do not stop taking Rybelsus without medical guidance, as these symptoms require urgent assessment to determine the cause and appropriate treatment.
All medical content on this blog is created based on reputable, evidence-based sources and reviewed regularly for accuracy and relevance. While we strive to keep content up to date with the latest research and clinical guidelines, it is intended for general informational purposes only.
DisclaimerThis content is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional with any medical questions or concerns. Use of the information is at your own risk, and we are not responsible for any consequences resulting from its use.
