Can Saxenda cause thyroid cancer? This question concerns many patients considering liraglutide 3.0 mg for weight management. Saxenda is a GLP-1 receptor agonist licensed in the UK for adults with obesity or overweight with comorbidities. Concerns arose from rodent studies showing thyroid C-cell tumours, but a causal link between Saxenda and thyroid cancer in humans has not been established. Human thyroid C-cells express far fewer GLP-1 receptors than rodents, and clinical trials involving over 5,000 participants reported no cases of medullary thyroid carcinoma. UK regulatory guidance advises caution in patients with personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2, reflecting a precautionary approach based on theoretical rather than proven risk.

Understanding Saxenda and Thyroid Cancer Concerns

Saxenda (liraglutide 3.0 mg) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for weight management in adults with a BMI ≥30 kg/m², or ≥27-<30 kg/m² with at least one weight-related comorbidity (such as prediabetes, type 2 diabetes, hypertension, dyslipidaemia or obstructive sleep apnoea). It is used as an adjunct to a reduced-calorie diet and increased physical activity.

Whilst Saxenda has demonstrated efficacy in promoting weight loss, concerns have been raised regarding a potential association with thyroid tumours, specifically medullary thyroid carcinoma (MTC).

These concerns originate from preclinical studies in rodents, where liraglutide and other GLP-1 receptor agonists were associated with an increased incidence of thyroid C-cell tumours. Rodent thyroid C-cells express high levels of GLP-1 receptors and appear particularly susceptible to stimulation by these agents. However, it is important to understand that a causal link between Saxenda and thyroid cancer in humans has not been established. The relevance of rodent findings to human physiology remains uncertain, as human thyroid C-cells express significantly lower levels of GLP-1 receptors compared to rodents.

The Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have reviewed the available evidence extensively. The UK Summary of Product Characteristics (SmPC) advises that Saxenda should be used with caution in patients with a personal or family history of medullary thyroid carcinoma or in those with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). This reflects a cautious regulatory approach based on the theoretical risk. Healthcare professionals prescribing Saxenda must carefully screen patients for these risk factors before initiating treatment, and patients should be informed about the theoretical concerns whilst understanding the current evidence base.

Clinical Evidence: Saxenda and Thyroid Tumour Risk

Clinical trial data from the SCALE (Satiety and Clinical Adiposity – Liraglutide Evidence) programme, which formed the basis for Saxenda's approval, included over 5,000 participants followed for up to three years. Throughout these studies, no cases of MTC were reported in liraglutide-treated patients. However, it's important to note that clinical trials have limited power to detect very rare events, particularly for a condition as uncommon as MTC.

Post-marketing surveillance data and real-world evidence have provided mixed signals, though a definitive causal relationship between GLP-1 receptor agonists and thyroid cancer in humans has not been established. While some observational studies have not identified a statistically significant increased risk, others have reported potential signals that require further investigation. Pharmacovigilance databases continue to monitor for any emerging patterns.

Medullary thyroid carcinoma is an extremely rare malignancy in the UK, accounting for only 3–4% of all thyroid cancers. According to Cancer Research UK data, the baseline incidence of MTC in the general population is very low. Given this rarity, detecting a potential association would require very large study populations followed over extended periods. Current evidence suggests that if any risk exists, it is likely to be very small and may not be distinguishable from background rates.

The mechanism of action of liraglutide involves activation of GLP-1 receptors, which are predominantly expressed in pancreatic beta cells, the gastrointestinal tract, and certain brain regions. The low expression of these receptors on human thyroid C-cells provides biological plausibility for the apparent lack of significant thyroid tumour risk in clinical practice, contrasting with the rodent model findings.

Who Should Use Saxenda with Caution Due to Thyroid Risk

According to the UK Summary of Product Characteristics (SmPC), Saxenda should be used with caution in specific patient groups due to theoretical thyroid cancer concerns. The human relevance of non-clinical thyroid C-cell tumours observed in rodents has not been confirmed but cannot be completely ruled out.

Patients with a personal history of medullary thyroid carcinoma (MTC) should generally avoid Saxenda, and alternative weight management approaches should be considered. This cautious approach is based on the theoretical possibility that stimulation of any residual C-cells could potentially influence disease recurrence, although this has not been demonstrated in clinical practice.

Individuals with a family history of medullary thyroid carcinoma should also use Saxenda with extreme caution, if at all. MTC can occur sporadically or as part of hereditary syndromes, and first-degree relatives of affected individuals have an elevated baseline risk. Healthcare professionals should specifically enquire about any family history of thyroid cancer during the prescribing assessment.

Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) represents another situation where Saxenda should generally be avoided. MEN 2 is a hereditary condition characterised by medullary thyroid carcinoma, phaeochromocytoma, and parathyroid abnormalities. Patients with known MEN 2 or those with genetic mutations associated with this syndrome (such as RET proto-oncogene mutations) should discuss alternative weight management strategies with their healthcare team. Clinicians should maintain a high index of suspicion for MEN 2 in patients presenting with relevant family histories or clinical features.

Before prescribing Saxenda, healthcare professionals should:

• Conduct a thorough medical and family history focusing on thyroid disorders and endocrine tumours

• Screen for symptoms suggestive of thyroid disease

• Document the risk assessment in the patient's medical records

• Provide clear patient information about the theoretical risks and the importance of reporting new symptoms

Patients with a history of other thyroid conditions, such as papillary or follicular thyroid cancer, benign thyroid nodules, or autoimmune thyroid disease, are not specifically advised against using Saxenda, though individual clinical assessment is warranted.

Recognising Thyroid Cancer Symptoms While Taking Saxenda

Whilst there is no established causal link between Saxenda and thyroid cancer in humans, patients and healthcare professionals should remain vigilant for symptoms that could indicate thyroid pathology. Early detection of thyroid cancer significantly improves treatment outcomes, making symptom awareness important regardless of medication use.

Key symptoms that warrant medical evaluation include:

• A palpable lump or swelling in the neck, particularly in the anterior (front) region where the thyroid gland is located

• Persistent hoarseness or voice changes lasting more than three weeks, which may indicate recurrent laryngeal nerve involvement

• Difficulty swallowing (dysphagia) or a sensation of something stuck in the throat

• Unexplained persistent cough not associated with respiratory infection

• Breathing difficulties or stridor, suggesting tracheal compression

• Neck or throat pain that may radiate to the ears

Patients taking Saxenda should be advised to contact their GP promptly if they develop any of these symptoms. It is important to emphasise that these symptoms are non-specific and far more commonly caused by benign conditions such as thyroid nodules, goitre, or upper respiratory tract infections. However, any persistent neck lump or concerning symptom requires clinical assessment.

Medullary thyroid carcinoma specifically may present with additional features including diarrhoea (due to calcitonin secretion) and flushing. In the context of MEN 2 syndrome, patients might also experience symptoms related to phaeochromocytoma, such as episodic hypertension, palpitations, and sweating.

Clinical examination by a GP should include palpation of the thyroid gland and cervical lymph nodes. If a thyroid nodule is detected, referral for further investigation is appropriate. According to NICE guideline NG12 (Suspected cancer: recognition and referral), patients with an unexplained thyroid lump should be referred using a suspected cancer pathway, with an appointment within two weeks. Investigations typically include thyroid function tests, ultrasound imaging, and fine-needle aspiration cytology for suspicious nodules. Calcitonin testing may be arranged in secondary care if MTC is specifically suspected.

UK Prescribing Guidelines and Safety Monitoring

UK prescribing guidelines for Saxenda emphasise careful patient selection and ongoing safety monitoring. The Summary of Product Characteristics (SmPC) approved by the MHRA provides comprehensive prescribing information, including the warnings related to thyroid cancer risk.

In the UK, Saxenda is recommended by NICE (Technology Appraisal TA664) as an option for weight management within a specialist weight management service for adults with a BMI of at least 35 kg/m² (or at least 32.5 kg/m² for members of minority ethnic groups known to be at equivalent risk of complications at a lower BMI) and at least one weight-related comorbidity. Treatment should be initiated by specialist multidisciplinary tier 3 services and can be continued for a maximum of 2 years.

Before initiating Saxenda treatment, prescribers must:

• Verify the absence of risk factors that warrant caution, particularly personal or family history of MTC or MEN 2

• Assess baseline thyroid status through clinical examination; routine thyroid function testing is not mandatory but may be considered based on clinical judgement

• Provide comprehensive patient counselling about potential adverse effects, including theoretical thyroid concerns

• Ensure patients understand when to seek medical attention for concerning symptoms

Ongoing monitoring during Saxenda treatment should include regular clinical review, typically at intervals of 4–12 weeks initially, then less frequently once stable. At each review, healthcare professionals should enquire about new symptoms, including those potentially related to thyroid pathology. Routine calcitonin monitoring is not recommended in the UK for patients taking Saxenda, as the clinical utility of such screening has not been established and may lead to unnecessary investigations.

According to the SmPC, treatment should be discontinued if patients do not achieve at least 5% weight loss after 12 weeks on the maintenance dose of 3.0 mg daily.

Suspected adverse reactions, including any cases of thyroid cancer diagnosed in patients taking Saxenda, should be reported via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk). This post-marketing surveillance remains crucial for detecting rare adverse events that may not be apparent in clinical trials.

Patients should be advised to inform all healthcare providers that they are taking Saxenda, particularly if they require thyroid investigations or develop thyroid-related symptoms. If thyroid surgery or other interventions become necessary, decisions about continuing or discontinuing Saxenda should be made collaboratively between the prescriber, endocrinologist, and patient, based on individual clinical circumstances.

Frequently Asked Questions