Key facts
- Rodent signal: GLP-1 RAs caused medullary thyroid carcinoma (MTC) in rats and mice at supratherapeutic doses over their lifetimes
- Human relevance uncertain: Human thyroid C-cells express far fewer GLP-1 receptors than rodent C-cells; large clinical trials have not confirmed an increased MTC risk in people
- Contraindication: GLP-1 RAs are contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia type 2 (MEN2)
- MHRA position: Warning remains on labels as a precaution; no specific safety alert issued for human thyroid cancer risk
- Common thyroid conditions: Hypothyroidism and Hashimoto’s thyroiditis are not contraindications
Where the concern comes from: rodent studies
Before any medication reaches patients, it undergoes extensive preclinical testing in animals. During the development of liraglutide (the active ingredient in Victoza and Saxenda), researchers observed that rats and mice exposed to the drug for their entire lifetimes developed tumours of the thyroid C-cells, including medullary thyroid carcinoma. The same finding was later observed with semaglutide (Ozempic, Wegovy) and other GLP-1 receptor agonists.
These findings were dose-dependent: higher doses and longer exposure led to a greater incidence of C-cell tumours. The lowest doses tested in rats were still higher, on a body-weight-adjusted basis, than the doses used in humans. The studies used lifetime exposure (approximately two years in rodents), which is proportionally much longer than typical human treatment durations.
Why rodent thyroid C-cells are different from human C-cells
A critical distinction is that rodent thyroid C-cells and human thyroid C-cells differ significantly in their biology:
- GLP-1 receptor expression: Rodent C-cells abundantly express GLP-1 receptors, making them highly responsive to GLP-1 RA stimulation. Human C-cells express these receptors at much lower levels, or not at all in some studies.
- Calcitonin response: In rodents, GLP-1 RAs cause a significant increase in serum calcitonin (a biomarker of C-cell activity). In human clinical trials, no clinically meaningful increase in calcitonin has been observed at therapeutic doses.
- C-cell proliferation: Rodent C-cells are inherently more prone to proliferation and neoplastic transformation. This is a known species difference that affects the interpretation of many drug safety studies.
Species difference matters: Regulatory agencies worldwide, including the MHRA and EMA, recognise that rodent C-cell tumour findings do not automatically predict human risk. The biological differences in GLP-1 receptor expression between species are a key factor in their risk assessment.
What the human data shows
Clinical trial evidence
The large cardiovascular outcome trials (CVOTs) for GLP-1 RAs — including SUSTAIN-6 (semaglutide), LEADER (liraglutide), REWIND (dulaglutide) and SURPASS (tirzepatide) — enrolled tens of thousands of patients with follow-up periods of two to five years. None of these trials identified a statistically significant increase in MTC or thyroid cancer incidence in patients randomised to a GLP-1 RA compared with placebo.
Importantly, the relatively low incidence of MTC (approximately 0.5 to 1.0 cases per 100,000 per year in the UK general population) means that even large clinical trials may not have sufficient statistical power to detect a small increase in risk. This is why ongoing pharmacovigilance is essential.
Observational and pharmacovigilance data
Several large observational studies using healthcare databases have examined the association between GLP-1 RA use and thyroid cancer:
- A 2023 study using French national health insurance data found a modestly increased signal for thyroid cancer overall in GLP-1 RA users, but the increase was driven primarily by papillary and follicular thyroid cancers (the most common types, unrelated to C-cells), not MTC. The authors noted that increased medical surveillance in GLP-1 RA users (more frequent doctor visits, potential detection bias) could explain this finding.
- A US FDA Sentinel System analysis found no significant increase in MTC risk with GLP-1 RA use over a median follow-up of approximately three years.
- The EMA and MHRA continue to monitor post-marketing reports. As of 2026, neither agency has changed its assessment that the available evidence does not confirm an increased MTC risk in humans.
The MEN2 and MTC contraindication
Absolute contraindication: GLP-1 receptor agonists must not be used in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2). This applies to all GLP-1 RAs: semaglutide, liraglutide, dulaglutide, exenatide and tirzepatide.
What is MEN2?
Multiple Endocrine Neoplasia type 2 is a rare inherited condition caused by mutations in the RET proto-oncogene. It is characterised by a very high lifetime risk of medullary thyroid carcinoma, along with phaeochromocytoma (adrenal tumours) and, in MEN2A, parathyroid adenomas. MEN2 is rare, affecting approximately 1 in 30,000 people.
If you have a family history of thyroid cancer, particularly if it was diagnosed at a young age or was specifically identified as medullary thyroid carcinoma, inform your prescriber before starting any GLP-1 medication. Genetic testing for RET mutations may be appropriate.
Other thyroid conditions: generally not a barrier
It is important to distinguish MTC and MEN2 from far more common thyroid conditions:
| Condition | GLP-1 RA use | Notes |
|---|---|---|
| Hypothyroidism (underactive thyroid) | Generally safe | Continue levothyroxine as normal; no dose adjustment needed for GLP-1 RA |
| Hashimoto’s thyroiditis | Generally safe | Autoimmune thyroiditis is not related to C-cell tumours |
| Graves' disease / hyperthyroidism | Generally safe | Discuss with endocrinologist if thyroid function is unstable |
| Previous papillary or follicular thyroid cancer | Generally safe | These arise from follicular cells, not C-cells; discuss with oncologist |
| Thyroid nodules | Investigate first | Ensure nodules are assessed before starting; MTC should be excluded |
| MTC or MEN2 | Contraindicated | Do not use any GLP-1 RA |
MHRA and EMA regulatory position
The MHRA requires all GLP-1 RA product labels to carry a warning about the rodent C-cell tumour findings and the MTC/MEN2 contraindication. This is a precautionary measure based on the animal data, consistent with the approach taken by the EMA and the US FDA.
Neither the MHRA nor the EMA has issued a Drug Safety Update or safety alert stating that GLP-1 RAs cause thyroid cancer in humans. Their position, as of April 2026, is that:
- The rodent findings are noted and communicated to prescribers and patients
- The contraindication in MTC/MEN2 remains appropriate
- Available human data (clinical trials + pharmacovigilance) does not confirm an increased risk of MTC
- Ongoing monitoring continues through the Yellow Card Scheme and EudraVigilance
Symptoms to watch for
Whilst routine thyroid screening is not recommended solely because you take a GLP-1 RA, you should be aware of symptoms that may indicate a thyroid problem and report them to your GP promptly:
- A new lump or swelling in the front of the neck
- Difficulty swallowing or a feeling of something stuck in the throat
- Persistent hoarseness or voice changes lasting more than three weeks
- Unexplained shortness of breath
- Persistent diarrhoea or flushing (can be associated with MTC in rare cases)
Practical advice: These symptoms are far more commonly caused by benign conditions (such as thyroid nodules, laryngitis or acid reflux from GLP-1 side effects) than by thyroid cancer. However, any persistent new symptom should be assessed by your GP. Early investigation provides reassurance and, in the rare event of a serious finding, enables prompt treatment.
Should calcitonin be monitored?
Calcitonin is a hormone produced by thyroid C-cells and is used as a tumour marker for MTC. In the United States, the FDA boxed warning led some clinicians to consider baseline calcitonin testing before starting GLP-1 RAs. However, routine calcitonin screening is not standard practice in the UK for several reasons:
- False positives are common: calcitonin can be elevated by proton pump inhibitors, chronic kidney disease, smoking and other conditions
- The baseline incidence of MTC is extremely low
- NICE and the BNF do not recommend routine calcitonin monitoring for GLP-1 RA users
- Elevated calcitonin in the absence of symptoms can trigger unnecessary anxiety, further testing and even unnecessary surgery
If you have a known family history of MTC or MEN2, calcitonin monitoring is part of standard care for that condition, irrespective of GLP-1 RA use — and you should not be prescribed a GLP-1 RA in the first place.
Frequently asked questions
Do GLP-1 medications cause thyroid cancer in humans?
There is no confirmed causal link. The concern originates from rodent studies where semaglutide and liraglutide caused medullary thyroid carcinoma in rats and mice at high doses. Human thyroid C-cells express far fewer GLP-1 receptors. Large clinical trials and pharmacovigilance data have not demonstrated an increased risk of MTC in people.
What is medullary thyroid carcinoma and why is it relevant to GLP-1?
MTC is a rare thyroid cancer arising from C-cells, accounting for approximately 3 to 5 per cent of all thyroid cancers in the UK. GLP-1 RAs stimulated C-cell growth in rodents, leading to a precautionary contraindication in patients with a personal or family history of MTC or MEN2.
What is the MHRA's position on GLP-1 and thyroid risk?
The MHRA requires a label warning based on the rodent findings and maintains the contraindication for MTC/MEN2. No specific safety alert has been issued linking GLP-1 RAs to thyroid cancer in humans. Monitoring continues through the Yellow Card Scheme.
Can I take Ozempic or Wegovy if I have a thyroid condition?
Common conditions such as hypothyroidism or Hashimoto’s thyroiditis are not contraindications. The restriction applies specifically to medullary thyroid carcinoma and MEN2. Discuss any thyroid history with your prescriber before starting treatment. See our guides on Ozempic and Wegovy for more details.
Should I have thyroid monitoring while on a GLP-1 medication?
Routine thyroid screening is not recommended solely for GLP-1 RA users. Report any new neck lump, difficulty swallowing, persistent hoarseness or unexplained shortness of breath to your GP for assessment.
Related guides
Sources
- MHRA — Ozempic and Wegovy Summary of Product Characteristics (SmPC)
- EMA — Assessment report: Ozempic (semaglutide), EPAR (ema.europa.eu)
- BNF — Semaglutide, Liraglutide, Tirzepatide monographs (bnf.nice.org.uk)
- Bjerre Knudsen L et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010; 151(4):1473-1486
- Bezin J et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care 2023; 46(2):384-390
- Marso SP et al. SUSTAIN-6: Semaglutide and Cardiovascular Outcomes. N Engl J Med 2016; 375:1834-1844
- Cancer Research UK — Thyroid cancer statistics (cancerresearchuk.org)
- NHS — Thyroid cancer (nhs.uk/conditions/thyroid-cancer)