GLP-1 receptor agonists such as semaglutide, liraglutide, and dulaglutide are increasingly prescribed for type 2 diabetes and weight management in the UK. As their use expands, patients and clinicians naturally question potential adverse effects, including whether these medications increase the risk of blood clots. Current evidence from large cardiovascular outcome trials and regulatory reviews does not support a direct link between GLP-1 agonists and thrombotic events. In fact, these drugs have demonstrated cardiovascular protective effects. This article examines the relationship between GLP-1 therapy and clotting risk, explores underlying patient risk factors, and provides guidance on recognising thrombotic symptoms.

What Are GLP-1 Receptor Agonists?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily used to manage type 2 diabetes mellitus and, more recently, obesity. These drugs mimic the action of the naturally occurring incretin hormone GLP-1, which is released from the intestine in response to food intake. By binding to GLP-1 receptors, these medications enhance glucose-dependent insulin secretion from pancreatic beta cells, suppress inappropriate glucagon release, slow gastric emptying, and promote satiety through central nervous system pathways.

Commonly prescribed GLP-1 receptor agonists available in the UK include:

• Exenatide (Byetta, Bydureon)

• Liraglutide (Victoza for diabetes; Saxenda for weight management)

• Dulaglutide (Trulicity)

• Semaglutide (Ozempic and Rybelsus for diabetes; Wegovy for weight management)

• Tirzepatide (Mounjaro), which is a dual GIP/GLP-1 receptor agonist

Most of these agents are administered via subcutaneous injection, with dosing frequencies ranging from twice daily to once weekly depending on the specific formulation. Semaglutide is also available as an oral tablet (Rybelsus).

NICE guidelines recommend GLP-1 receptor agonists as add-on therapy for type 2 diabetes when glycaemic targets are not met with other treatments. They are typically used when specific criteria are met, including BMI thresholds (≥30 kg/m² in most people) or weight-related problems. For weight management, NICE recommends these medications as an adjunct to lifestyle modification in specialist weight management services, with specific BMI thresholds (typically ≥35 kg/m² or ≥32.5 kg/m² in certain ethnic groups) with comorbidities, and usually for time-limited periods (up to 2 years for semaglutide).

The mechanism of action does not directly involve the coagulation cascade or platelet function, which has led to questions about whether these medications might influence thrombotic risk. Understanding the cardiovascular profile of GLP-1 agonists is essential for both prescribers and patients, particularly given the metabolic conditions they are used to treat often carry inherent cardiovascular risk.

Cardiovascular Effects of GLP-1 Drugs

There is no established direct link between GLP-1 receptor agonists and an increased risk of blood clots (venous thromboembolism or arterial thrombosis). In fact, extensive cardiovascular outcome trials have demonstrated that several GLP-1 agonists provide cardiovascular benefits rather than harm. Landmark studies such as LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide) have shown significant reductions in major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, in patients with type 2 diabetes and established cardiovascular disease or multiple risk factors.

The cardiovascular protective mechanisms of GLP-1 receptor agonists are thought to include:

• Improved glycaemic control, reducing endothelial dysfunction associated with hyperglycaemia

• Weight reduction, decreasing metabolic stress and inflammation

• Blood pressure lowering, potentially through effects on fluid balance and vascular function

• Favourable lipid profile changes, including modest reductions in LDL cholesterol and triglycerides

• Anti-inflammatory effects, reducing systemic markers of inflammation such as C-reactive protein

Regulatory bodies including the MHRA and EMA have not identified thrombotic events as a specific safety concern with GLP-1 receptor agonists. The Summary of Product Characteristics (SmPC) for these medications does not currently list blood clots as a recognised adverse effect. Ongoing pharmacovigilance continues to monitor the safety profile of these medications.

It is important to recognise that patients prescribed GLP-1 agonists often have underlying conditions—such as type 2 diabetes, obesity, hypertension, and dyslipidaemia—that independently increase cardiovascular and thrombotic risk. Any thrombotic events occurring in this population are more likely related to these pre-existing risk factors rather than the medication itself.

Risk Factors for Blood Clots While Taking GLP-1 Agonists

While GLP-1 receptor agonists do not directly cause blood clots, patients taking these medications may have multiple independent risk factors for thromboembolism that warrant clinical attention. Understanding these risk factors is essential for comprehensive patient management and appropriate risk stratification.

Established risk factors for venous thromboembolism (VTE) include:

• Obesity (BMI ≥30 kg/m²), which increases venous stasis and pro-inflammatory states

• Immobility or reduced mobility, particularly relevant in patients with severe obesity

• Previous history of VTE or family history of thrombophilia

• Active malignancy or recent surgery

• Hormonal therapies, including combined oral contraceptives or hormone replacement therapy

• Pregnancy and the postpartum period

• Smoking, which affects endothelial function and coagulation

Risk factors for arterial thrombosis (myocardial infarction, stroke) include:

• Type 2 diabetes mellitus, associated with endothelial dysfunction, platelet hyperreactivity, and a prothrombotic state

• Hypertension, causing arterial wall damage

• Dyslipidaemia, promoting atherosclerotic plaque formation

• Established cardiovascular disease

• Chronic kidney disease, common in diabetes and associated with increased cardiovascular risk

Patients initiating GLP-1 therapy should undergo a comprehensive cardiovascular risk assessment. NICE recommends using tools such as QRISK3 to estimate 10-year cardiovascular disease risk. Those identified as high risk may benefit from preventive strategies including statin therapy and lifestyle modifications, as per NICE guidance on cardiovascular disease prevention. Antiplatelet therapy (such as aspirin) is generally reserved for those with established cardiovascular disease or other specific indications, rather than for primary prevention.

It is worth noting that the weight loss and metabolic improvements achieved with GLP-1 agonists may actually reduce overall thrombotic risk over time by addressing several modifiable risk factors. However, individual patient circumstances should always be considered, and any concerns about thrombotic risk should be discussed with the prescribing clinician.

When to Seek Medical Advice

Patients taking GLP-1 receptor agonists should be educated about the signs and symptoms of potential thrombotic events, even though these are not caused by the medication itself. Early recognition and prompt medical attention can be life-saving.

Seek immediate medical attention (call 999 or attend A&E) if you experience:

• Chest pain or tightness, particularly if radiating to the arm, jaw, or back (possible myocardial infarction)

• Sudden breathlessness or difficulty breathing, especially with chest pain or coughing up blood (possible pulmonary embolism)

• Sudden weakness, numbness, or paralysis affecting one side of the body, face drooping, or speech difficulties (possible stroke)

• Severe leg pain, swelling, warmth, or redness, particularly in one calf (possible deep vein thrombosis)

• Sudden severe headache unlike any previously experienced

• Visual disturbances, including sudden loss of vision or double vision

Contact your GP or diabetes specialist nurse if you notice:

• Persistent or worsening leg swelling

• Unexplained shortness of breath on exertion

• New or worsening chest discomfort

• Concerns about your cardiovascular risk factors

Patients should also be aware of common side effects of GLP-1 agonists, which are unrelated to blood clots but may cause concern. These include gastrointestinal symptoms (nausea, vomiting, diarrhoea, constipation), injection site reactions, and, rarely, pancreatitis (severe upper abdominal pain radiating to the back) or gallbladder problems. Any severe or persistent side effects should be reported to your healthcare provider and can also be reported through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

Regular monitoring is essential for patients on GLP-1 therapy. This typically includes periodic assessment of HbA1c, renal function, and cardiovascular risk factors. Maintaining open communication with your healthcare team, attending scheduled appointments, and reporting any new or concerning symptoms promptly will help ensure safe and effective treatment. If you have specific concerns about thrombotic risk, discuss your individual risk profile with your GP or diabetes specialist, who can provide personalised advice and, if necessary, arrange appropriate investigations or referrals.

Frequently Asked Questions