Does Victoza cause thyroid cancer? This question concerns many patients prescribed liraglutide for type 2 diabetes. Victoza (liraglutide) is a GLP-1 receptor agonist that improves blood glucose control and reduces cardiovascular risk. Concerns arose from animal studies showing thyroid C-cell tumours in rodents, prompting regulatory warnings. However, extensive human clinical trials and real-world data spanning over a decade have not established a causal link between Victoza and thyroid cancer. Rodent thyroid physiology differs significantly from humans, making direct comparisons problematic. This article examines the evidence, regulatory guidance, and practical considerations for patients and healthcare professionals in the UK.

Understanding Victoza and Thyroid Cancer Concerns

Victoza (liraglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for the treatment of type 2 diabetes mellitus, including for cardiovascular risk reduction in adults with type 2 diabetes and established cardiovascular disease. It works by mimicking the action of the naturally occurring hormone GLP-1, which stimulates insulin secretion in response to food intake, suppresses glucagon release, and slows gastric emptying. These combined effects help to improve glycaemic control.

Concerns about a potential link between Victoza and thyroid cancer emerged from preclinical animal studies conducted during the drug's development. In rodent models, particularly rats and mice, liraglutide was associated with an increased incidence of thyroid C-cell tumours (medullary thyroid carcinoma, or MTC) at clinically relevant and higher doses. These findings prompted regulatory authorities, including the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, to include specific warnings in the product information.

It is crucial to understand that rodent thyroid physiology differs significantly from that of humans. Rats and mice have a much higher density of GLP-1 receptors on thyroid C-cells compared to humans, making them more susceptible to C-cell proliferation when exposed to GLP-1 agonists. Despite extensive post-marketing surveillance and clinical trial data spanning over a decade, there is no established causal link between liraglutide use and thyroid cancer in humans. Nevertheless, the theoretical risk identified in animal studies has led to important warnings and monitoring recommendations for patients receiving Victoza.

Note that for weight management, a higher dose formulation of liraglutide (3mg) is marketed as Saxenda in the UK, which carries similar thyroid-related warnings.

Clinical Evidence: Victoza and Thyroid Tumour Risk

The clinical evidence base for Victoza's safety profile in relation to thyroid cancer comes from large-scale randomised controlled trials and real-world observational studies. The landmark LEADER trial (New England Journal of Medicine, 2016), which followed over 9,000 patients with type 2 diabetes for a median of 3.8 years, found no significant increase in thyroid cancer cases among those treated with liraglutide compared to placebo. Similarly, the SCALE obesity trials (NEJM, 2015), which evaluated higher doses of liraglutide for weight management, reported no excess thyroid malignancies.

Post-marketing pharmacovigilance data from multiple countries, including the UK, has not demonstrated a clear signal for increased thyroid cancer risk in humans taking Victoza, though the data are mixed and limited by follow-up duration and the rarity of medullary thyroid carcinoma. A review of adverse event reporting systems found that reported cases of medullary thyroid carcinoma in liraglutide users were extremely rare and occurred at rates consistent with background population incidence. Many reported cases had pre-existing risk factors or were diagnosed shortly after treatment initiation, suggesting the cancer was likely present before liraglutide exposure.

Population-based cohort studies have provided further reassurance. A large Danish registry study examining patients treated with GLP-1 receptor agonists, including liraglutide, found no increased risk of thyroid cancer compared to other diabetes medications. However, researchers acknowledge that longer follow-up periods may be necessary to detect rare malignancies with long latency periods.

The current consensus among endocrinologists and regulatory bodies is that whilst animal data warrant caution, human evidence does not support a causal relationship between Victoza and thyroid cancer. It is important to note that routine calcitonin or ultrasound screening for medullary thyroid carcinoma is not recommended in the UK product information for patients taking Victoza.

MHRA and Regulatory Warnings for Victoza

In the UK, the MHRA is the regulatory authority responsible for medicines safety. The Summary of Product Characteristics (SmPC) for Victoza contains warnings in section 4.4 (Special warnings and precautions for use) regarding thyroid C-cell tumours observed in rodent studies. The SmPC states that the relevance of these findings to humans is unknown, but advises that patients should be counselled on the symptoms of thyroid tumours.

Unlike in the United States, where the FDA requires a boxed warning and contraindications for patients with personal or family history of MTC or MEN2, the UK SmPC for Victoza does not include these as formal contraindications. In the UK, Victoza is contraindicated only in cases of hypersensitivity to liraglutide or any of the excipients.

Nevertheless, the SmPC advises healthcare professionals to consider the potential risks and benefits of liraglutide treatment carefully in patients with thyroid disease. The warnings reflect a precautionary approach based on the animal data, despite the lack of confirmed human risk.

Healthcare professionals are expected to inform patients about the symptoms of thyroid tumours and advise them to report any neck swelling, persistent hoarseness, difficulty swallowing, or shortness of breath. The MHRA monitors safety data through the Yellow Card reporting scheme, and both healthcare professionals and patients are encouraged to report any suspected adverse reactions associated with Victoza use via yellowcard.mhra.gov.uk.

Patients should be reassured that while these warnings exist as a precaution, the extensive clinical trial and real-world data have not established a causal link between Victoza and thyroid cancer in humans. Open communication between patients and healthcare providers about both the benefits of improved glycaemic control and cardiovascular risk reduction, alongside the theoretical risks, is essential for informed decision-making.

Symptoms and Warning Signs to Monitor

Whilst the risk of thyroid cancer associated with Victoza remains theoretical in humans, patients taking this medication should be aware of key symptoms that warrant prompt medical evaluation. Medullary thyroid carcinoma, the specific type of thyroid cancer observed in animal studies, often presents with a palpable neck mass or nodule. Patients should be aware of the symptoms that might indicate a thyroid problem and seek medical advice if they develop.

Common warning signs of thyroid tumours include:

• Persistent hoarseness or voice changes lasting more than two weeks

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

• Unexplained neck pain or discomfort, particularly if localised to one side

• Persistent cough not associated with respiratory infection

• Shortness of breath or noisy breathing (stridor) in advanced cases

• Visible neck swelling or asymmetry

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 infections. However, given the warnings associated with Victoza, any patient experiencing these symptoms should seek medical assessment promptly.

If you develop concerning symptoms, your GP will conduct a thorough clinical examination. According to NICE guideline NG12 (Suspected cancer: recognition and referral), if thyroid cancer is suspected, you should be referred on an urgent suspected cancer pathway to a specialist, who may arrange further investigations such as thyroid ultrasound and possible fine-needle aspiration biopsy. NICE guideline NG230 (Thyroid cancer: assessment and management) provides further guidance on the assessment and management of thyroid cancer in secondary care.

Patients should also report any family history of thyroid cancer that was not previously disclosed, as this may necessitate reassessment of Victoza's suitability. Regular diabetes review appointments provide an opportunity to discuss any new symptoms or concerns.

Who Should Exercise Caution with Victoza

In the UK, Victoza is formally contraindicated only in patients with hypersensitivity to liraglutide or any of the excipients, as stated in the Summary of Product Characteristics. However, based on the preclinical findings and warnings in section 4.4 of the SmPC, certain patient groups should exercise particular caution and discuss the risks and benefits thoroughly with their healthcare provider.

Patients with a personal history of medullary thyroid carcinoma (MTC) should discuss alternative diabetes treatments with their healthcare provider. MTC accounts for approximately 3-4% of all thyroid cancers and arises from the parafollicular C-cells of the thyroid gland—the same cells that showed tumour development in rodent studies.

Individuals with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) represent another group where caution is advised. MEN 2 is a rare inherited disorder caused by mutations in the RET proto-oncogene, which dramatically increases the risk of MTC, often presenting at a young age. MEN 2 also predisposes to phaeochromocytoma and parathyroid tumours. Patients with MEN 2 typically undergo prophylactic thyroidectomy in childhood or early adulthood.

Patients with a family history of MTC or MEN 2 should inform their healthcare provider, as this may influence the risk-benefit assessment of Victoza therapy. Even though these are not formal contraindications in the UK (unlike in the US), specialist endocrinology input may be appropriate before initiating treatment.

Additionally, prescribers should exercise clinical judgement in patients with:

• Pre-existing thyroid nodules of uncertain significance

• Previous thyroid surgery for reasons other than MTC

• Elevated calcitonin levels (a tumour marker for C-cell disease)

Whilst routine calcitonin screening is not recommended in the UK for patients taking Victoza, any unexplained elevated calcitonin level should be evaluated according to standard clinical pathways. Patients in these categories should have a thorough discussion about the theoretical risk and alternative treatment options with their healthcare provider.

Safe Alternatives and Risk Management Strategies

For patients who wish to avoid Victoza due to thyroid cancer concerns, numerous effective alternatives exist for managing type 2 diabetes. The choice of alternative therapy should be individualised based on glycaemic control needs, cardiovascular risk profile, renal function, and patient preferences, in accordance with NICE guidance (NG28: Type 2 diabetes in adults).

Alternative GLP-1 receptor agonists such as dulaglutide (Trulicity), semaglutide (Ozempic), and exenatide (Byetta, Bydureon) carry similar warnings regarding thyroid C-cell tumours based on rodent data. Therefore, patients with specific concerns about MTC risk may wish to consider other medication classes.

SGLT2 inhibitors (sodium-glucose co-transporter-2 inhibitors) such as empagliflozin, dapagliflozin, and canagliflozin represent excellent alternatives, particularly for patients with heart failure or chronic kidney disease. These agents promote glucose excretion through the kidneys and provide modest weight loss benefits.

DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors) like sitagliptin, linagliptin, and saxagliptin offer another option. Whilst less potent than GLP-1 agonists for glycaemic control and weight reduction, they are well-tolerated and have no thyroid-related warnings.

For patients requiring injectable therapy, insulin remains the gold standard, with no thyroid cancer associations. Modern insulin analogues and delivery devices offer flexibility and effectiveness.

Risk management strategies for patients continuing Victoza include:

• Baseline assessment: Document personal and family history of thyroid disease and MEN 2

• Patient education: Provide information about warning symptoms to report

• Prompt investigation: If symptoms develop, make an urgent suspected cancer referral in line with NICE guideline NG12

• Shared decision-making: Ensure patients understand theoretical risks and provide informed consent

• Adverse event reporting: Report any suspected adverse reactions via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk)

Patients should maintain open communication with their diabetes care team and report any concerns promptly. The decision to continue or discontinue Victoza should be made collaboratively, weighing the proven benefits for diabetes control and cardiovascular protection against the theoretical thyroid cancer risk that has not been substantiated in human studies.

Frequently Asked Questions