Trulicity (dulaglutide) is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) widely prescribed in the UK for type 2 diabetes mellitus management. Concerns about Trulicity and thyroid cancer emerged from animal studies showing medullary thyroid carcinoma in rodents, prompting regulatory warnings and patient anxiety. However, human evidence remains reassuring, with large clinical trials finding no definitive causal link. Understanding the distinction between preclinical findings and clinical reality is essential for informed prescribing and patient counselling. This article examines the evidence, regulatory guidance, and practical considerations for healthcare professionals and patients using Trulicity.

What Is Trulicity and How Does It Work?

Trulicity (dulaglutide) is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) licensed in the UK for the treatment of type 2 diabetes mellitus. It is administered as a once-weekly subcutaneous injection and works by mimicking the action of the naturally occurring hormone GLP-1, which plays a crucial role in glucose regulation.

The mechanism of action involves several complementary pathways. Trulicity stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning insulin release occurs primarily when blood glucose levels are elevated. This reduces the risk of hypoglycaemia compared with some other diabetes medications. Additionally, it suppresses glucagon secretion from pancreatic alpha cells, slows gastric emptying to moderate postprandial glucose excursions, and may promote satiety, often leading to modest weight reduction.

Trulicity is available in several doses (0.75mg, 1.5mg, 3mg and 4.5mg) and is typically prescribed when metformin alone provides inadequate glycaemic control, or as part of combination therapy with other oral hypoglycaemic agents or insulin. It may also be considered if metformin is not tolerated or contraindicated. NICE guidance (NG28) supports the use of GLP-1 receptor agonists in specific clinical scenarios, particularly for patients with a body mass index (BMI) ≥35 kg/m² (or lower in certain ethnic groups or where weight loss would benefit obesity-related comorbidities) who have inadequate control despite optimised therapy.

The medication has demonstrated efficacy in reducing HbA1c levels, and the REWIND trial showed cardiovascular benefits, though it is important to note that Trulicity is not specifically licensed in the UK for cardiovascular risk reduction. Like all medications, Trulicity carries potential adverse effects and safety considerations. Understanding both the therapeutic benefits and the risk profile—including concerns about thyroid pathology—is essential for informed prescribing and patient counselling.

Clinical Evidence and Risk Assessment

Concerns regarding GLP-1 receptor agonists and thyroid cancer emerged from preclinical animal studies, particularly in rodents. Research demonstrated that prolonged exposure to GLP-1 RAs, including dulaglutide, caused C-cell hyperplasia and medullary thyroid carcinoma (MTC) in rats and mice. These findings led to regulatory warnings, as GLP-1 receptors are expressed on thyroid C-cells, which produce calcitonin.

However, translating animal data to human risk requires careful consideration. Rodents have substantially higher densities of GLP-1 receptors on thyroid C-cells compared with humans, where expression is low and variable. The clinical relevance of these differences remains uncertain. The rodent thyroid physiology differs significantly from humans, and the relevance of rodent thyroid tumours to human clinical practice continues to be debated within the endocrinology community.

Human epidemiological evidence has been generally reassuring but with some conflicting data. Large-scale randomised controlled trials and meta-analyses have not established a definitive causal link between GLP-1 receptor agonists and thyroid cancer in humans. The REWIND cardiovascular outcome trial, which followed patients for a median of 5.4 years, reported very low rates of thyroid neoplasms with no clear signal of increased risk. However, some observational studies, including a large French national database analysis, have reported a small potential increased risk, highlighting the need for continued monitoring.

The UK Summary of Product Characteristics (SmPC) for Trulicity notes that rodent C-cell tumours were observed in non-clinical studies but states that the relevance to humans is unknown. The SmPC does not list a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) as formal contraindications in the UK, though clinicians should consider individual patient risk factors when prescribing any medication.

MHRA Guidance and Safety Monitoring

The Medicines and Healthcare products Regulatory Agency (MHRA) provides regulatory oversight for Trulicity in the UK. According to the UK Summary of Product Characteristics (SmPC), the only formal contraindication for dulaglutide is hypersensitivity to the active substance or any of the excipients.

The UK product information notes that in non-clinical studies, dulaglutide caused thyroid C-cell tumours in rodents, but the relevance to humans is unknown. Unlike some international regulatory positions, the UK SmPC does not contraindicate use in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).

Nevertheless, as good clinical practice, healthcare professionals should take a thorough medical and family history before initiating treatment, specifically enquiring about thyroid disorders and relevant endocrine conditions.

Routine calcitonin monitoring is not recommended for patients receiving GLP-1 receptor agonists in standard UK clinical practice. Serum calcitonin is a tumour marker for medullary thyroid carcinoma, but its use as a screening tool in asymptomatic patients lacks specificity and can lead to unnecessary investigations. Elevated calcitonin levels may occur due to various benign conditions, including C-cell hyperplasia, chronic kidney disease, or other non-malignant thyroid pathology.

The MHRA encourages reporting of suspected adverse drug reactions through the Yellow Card scheme (yellowcard.mhra.gov.uk). This pharmacovigilance system enables ongoing safety monitoring and helps identify previously unrecognised risks.

Patient information leaflets accompanying Trulicity include information about thyroid tumours observed in animal studies. Whilst this may cause understandable concern, it is important that healthcare professionals contextualise this information, explaining the uncertain relevance to human patients whilst maintaining appropriate clinical vigilance.

When to Seek Medical Advice

Patients prescribed Trulicity should be educated about thyroid cancer symptoms, although it is important to emphasise that such malignancies are rare and there is no established causal relationship with dulaglutide in humans. Most thyroid nodules are benign. Awareness of potential warning signs enables early detection and appropriate investigation if concerns arise.

Key symptoms that warrant medical evaluation include:

• A palpable lump or swelling in the neck

• Persistent hoarseness or voice changes

• Difficulty swallowing (dysphagia)

• Difficulty breathing or a sensation of throat tightness

• Persistent cough unrelated to respiratory infection

• Unexplained neck or throat pain

Patients experiencing any of these symptoms should contact their GP promptly for clinical assessment. A thorough examination, including palpation of the thyroid gland and cervical lymph nodes, should be performed.

In line with NICE guidance on suspected cancer recognition and referral (NG12), an urgent suspected cancer referral (two-week wait) should be considered for patients with an unexplained thyroid lump or cervical lymphadenopathy, or with unexplained hoarseness or voice changes with a thyroid abnormality. Patients with a rapidly enlarging neck mass, associated suspicious lymphadenopathy, or thyroid nodules with concerning features should be referred urgently.

For less concerning presentations, urgent ultrasound may be appropriate to risk-stratify thyroid nodules, with fine-needle aspiration cytology guided by ultrasound findings. Emergency medical attention (999/A&E) is required for symptoms suggesting airway compromise, such as stridor or severe breathing difficulty.

It is equally important that patients do not discontinue Trulicity without medical advice due to anxiety about thyroid cancer risk. Abrupt cessation may lead to deterioration in glycaemic control, with associated risks of diabetic complications. Any concerns should be discussed with the prescribing clinician, who can provide individualised risk-benefit assessment.

Regular diabetes reviews provide opportunities to monitor for adverse effects and address patient concerns. Healthcare professionals should maintain an open dialogue about medication safety whilst reinforcing that current evidence does not support a significant thyroid cancer risk in humans.

Frequently Asked Questions