Does Tirzepatide Cause Blood Clots? UK Evidence Review

Tirzepatide (Mounjaro) is a dual GIP and GLP-1 receptor agonist licensed in the UK for type 2 diabetes and weight management. Concerns about blood clots naturally arise with metabolic medications, but current evidence provides reassurance. Clinical trial data and post-marketing surveillance have not identified thrombotic events as a characteristic adverse effect of tirzepatide. The MHRA and EMA continuously monitor its safety profile, with gastrointestinal symptoms remaining the most frequently reported side effects. However, patients with pre-existing cardiovascular risk factors require careful assessment. This article examines the evidence, explores indirect mechanisms that might theoretically affect clotting risk, and provides guidance on safe tirzepatide use in UK clinical practice.

Does Tirzepatide Cause Blood Clots?

There is currently no established direct causal link between tirzepatide and blood clot formation. Tirzepatide (marketed as Mounjaro) is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for type 2 diabetes management and weight loss. Whilst concerns about blood clots naturally arise with any medication affecting metabolism and weight, clinical trial data and post-marketing surveillance have not identified thrombotic events as a characteristic adverse effect of tirzepatide.

The Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) continuously monitor the safety profile of tirzepatide. According to the current MHRA-approved Summary of Product Characteristics (SmPC) for Mounjaro, venous thromboembolism (VTE) or arterial thrombosis are not listed among the adverse reactions. The most frequently reported side effects remain gastrointestinal in nature, including nausea, vomiting, diarrhoea, and constipation.

However, it is important to recognise that any significant weight loss treatment can indirectly influence cardiovascular and metabolic parameters. Patients with pre-existing risk factors for blood clots—such as obesity, immobility, previous thrombotic events, or certain medical conditions—require careful clinical assessment before and during treatment. Healthcare professionals should maintain vigilance for any unusual symptoms and ensure patients understand when to seek urgent medical attention.

Patients and healthcare professionals are encouraged to report any suspected adverse reactions to tirzepatide via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

This article examines the current evidence, explores potential indirect mechanisms that might theoretically affect clotting risk, and provides guidance on safe use of tirzepatide in clinical practice.

Understanding Tirzepatide and Cardiovascular Safety

Tirzepatide works through a novel dual-agonist mechanism, activating both GIP and GLP-1 receptors. This action enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and reduces appetite—leading to improved glycaemic control and substantial weight reduction. The medication is administered once weekly via subcutaneous injection, with doses in the UK starting at 2.5 mg and increasing in stepwise increments to 5 mg, 10 mg, and potentially 15 mg depending on therapeutic response and tolerability.

Cardiovascular outcomes have been a primary focus in tirzepatide clinical development. The SURPASS clinical trial programme, which included over 10,000 participants with type 2 diabetes, demonstrated favourable cardiovascular safety signals. Major adverse cardiovascular events (MACE)—comprising cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke—occurred at rates comparable to or lower than comparator treatments. The dedicated cardiovascular outcomes trial, SURPASS-CVOT, is ongoing and will provide definitive long-term data.

From a mechanistic perspective, tirzepatide's effects on weight loss, blood pressure reduction, and lipid profile improvement may theoretically reduce cardiovascular risk, including thrombotic events. Weight loss itself is associated with decreased inflammatory markers, improved endothelial function, and reduced prothrombotic factors such as plasminogen activator inhibitor-1 (PAI-1). However, definitive cardiovascular benefit awaits confirmation from the outcomes trial.

The MHRA-approved prescribing information notes that thyroid C-cell tumours have been observed in rodent studies (with uncertain human relevance) and advises patients to seek medical attention if they notice symptoms such as a neck mass, hoarseness, or difficulty swallowing. The SmPC also highlights monitoring for pancreatitis and diabetic retinopathy complications, but does not identify thrombotic risk as a specific concern. Clinicians should focus on comprehensive cardiovascular risk assessment as part of routine diabetes and obesity management rather than specific clotting concerns related to the medication itself.

Blood Clot Risk Factors During Weight Loss Treatment

Whilst tirzepatide itself does not appear to cause blood clots, the context of weight loss treatment requires consideration of several indirect factors that may influence thrombotic risk. Understanding these elements helps clinicians provide appropriate patient counselling and monitoring.

Obesity is itself a significant independent risk factor for venous thromboembolism. Excess adipose tissue promotes a pro-inflammatory state, increases circulating clotting factors, and impairs fibrinolysis. Patients commencing tirzepatide often have multiple cardiovascular risk factors including hypertension, dyslipidaemia, and reduced mobility—all of which contribute to baseline thrombotic risk before any treatment begins.

During rapid weight loss, several physiological changes occur:

• Dehydration risk: Gastrointestinal side effects (nausea, vomiting, diarrhoea) may lead to reduced fluid intake and dehydration, which can increase blood viscosity. Adequate hydration is essential throughout treatment.

• Medication interactions: Reduced food intake might affect vitamin K intake in patients taking warfarin, potentially requiring more frequent INR monitoring. The tirzepatide SmPC also notes that oral contraceptive efficacy may be reduced during initiation and dose escalation, suggesting additional contraceptive measures may be needed.

• Exogenous hormones: Combined hormonal contraceptives and hormone replacement therapy are established VTE risk factors that should be considered in the overall risk assessment.

• Increased physical activity: Gradual increases in physical activity are beneficial and should be encouraged in line with NHS guidance on safe exercise progression.

Immobility remains a critical concern. Patients who experience severe gastrointestinal side effects may reduce their activity levels temporarily, potentially increasing VTE risk. Healthcare professionals should encourage maintained mobility and consider thromboprophylaxis in specific high-risk scenarios such as prolonged hospitalisation or surgical procedures.

NICE guidance on VTE prevention (NG89) emphasises individual risk assessment using validated tools. Patients on tirzepatide should be evaluated for additional risk factors including active cancer, thrombophilia, recent surgery, or prolonged travel, with appropriate preventive measures implemented where indicated in accordance with NICE recommendations.

Clinical Evidence: Tirzepatide and Thrombotic Events

Analysis of clinical trial data provides reassurance regarding thrombotic safety, though studies were not specifically powered to assess VTE risk. The SURPASS programme (SURPASS 1-5) enrolled diverse patient populations with type 2 diabetes, including those with established cardiovascular disease. Across these studies, thrombotic events were monitored as part of routine adverse event reporting and cardiovascular safety assessments.

In the pivotal SURPASS-2 trial, which compared tirzepatide directly with semaglutide (another GLP-1 receptor agonist), no significant difference in thrombotic event rates was observed between treatment groups, though event numbers were low. Similarly, SURPASS-4, which specifically enrolled patients at high cardiovascular risk, demonstrated a numerical reduction in MACE with tirzepatide compared to insulin glargine, suggesting potential cardiovascular benefit, though definitive conclusions await the dedicated outcomes trial.

Post-marketing surveillance data has not identified a signal for increased blood clot risk with tirzepatide based on currently available regulatory information. However, absence of a signal does not exclude the possibility of rare events, and continued vigilance is warranted. Healthcare professionals and patients are encouraged to report any suspected adverse reactions via the MHRA Yellow Card scheme, contributing to ongoing safety monitoring.

Comparative data with other incretin-based therapies is also informative. GLP-1 receptor agonists as a class have not been associated with increased thrombotic risk; indeed, some studies suggest potential protective cardiovascular effects. Tirzepatide's dual mechanism does not introduce pharmacological properties that would be expected to promote coagulation.

It is important to distinguish correlation from causation. Patients with type 2 diabetes and obesity have inherently elevated baseline risk for cardiovascular events including thrombosis. Any thrombotic events occurring during tirzepatide treatment must be evaluated in this context, considering the patient's underlying risk profile, comorbidities, and concurrent medications.

Clinicians should maintain perspective: the substantial metabolic benefits of tirzepatide—including HbA1c reduction averaging 2.0-2.5% in type 2 diabetes trials (SURPASS) and weight loss of 15-20% in obesity trials (SURMOUNT)—may confer overall cardiovascular benefit that outweighs any theoretical concerns about clotting risk, though this requires confirmation from long-term outcome studies.

When to Seek Medical Advice While Taking Tirzepatide

Patient education about warning signs is essential for safe tirzepatide use. Whilst blood clots are not a recognised side effect of the medication, patients should be aware of symptoms requiring urgent medical assessment, particularly given their underlying cardiovascular risk factors.

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

• Signs of deep vein thrombosis (DVT): Painful swelling, warmth, and redness in one leg (usually the calf), particularly if accompanied by skin discolouration

• Symptoms of pulmonary embolism (PE): Sudden breathlessness, sharp chest pain (worse with breathing), rapid heart rate, coughing up blood, or feeling faint

• Indicators of stroke: Sudden weakness or numbness on one side of the body, facial drooping, slurred speech, severe headache, or vision changes

• Signs of myocardial infarction: Central chest pain or pressure, pain radiating to the arm, jaw or back, breathlessness, nausea, or sweating

Contact NHS 111 or your GP or diabetes specialist nurse promptly for:

• Persistent severe gastrointestinal symptoms leading to dehydration (reduced urination, dizziness, dry mouth)

• Unexplained persistent pain or swelling in the legs

• Unusual bruising or bleeding

• Any concerns about medication side effects

Routine monitoring during tirzepatide treatment should include regular review of cardiovascular risk factors, blood pressure measurement, and assessment of glycaemic control. Patients planning surgery should inform their surgical team about tirzepatide use. Current UK perioperative guidance generally allows continuation of GLP-1 receptor agonists, but patients should follow local hospital protocols and specialist advice, particularly if they have significant gastrointestinal symptoms.

For long-haul travel (flights over four hours), patients should follow standard NHS VTE prevention advice: maintain hydration, perform regular leg exercises, wear compression stockings if appropriate, and discuss with their GP whether additional precautions are needed based on individual risk factors.

Healthcare professionals should ensure patients understand that whilst tirzepatide does not cause blood clots, their underlying conditions may place them at risk. Maintaining prescribed medications, attending regular monitoring appointments, and promptly reporting concerning symptoms enables safe, effective treatment and optimal cardiovascular risk management.

Patients who experience any suspected side effects from tirzepatide should report them to the MHRA through the Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

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