Does Victoza Cause Thyroid Tumors?
Victoza (liraglutide) causes thyroid C-cell tumors in rodents at clinically relevant exposures, but the human relevance of these findings has not been determined and current evidence does not support an increased risk of thyroid cancer in humans. 1
FDA Black Box Warning and Contraindications
The FDA requires a black box warning for Victoza stating that liraglutide causes thyroid C-cell tumors in both male and female rats and mice, though it remains unknown whether this translates to medullary thyroid carcinoma (MTC) risk in humans. 1
Victoza is absolutely contraindicated in patients with: 2, 1
- Personal history of medullary thyroid carcinoma (MTC)
- Family history of MTC
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Patients should be counseled about potential thyroid tumor symptoms including neck lumps or swelling, hoarseness, trouble swallowing, or shortness of breath. 1
Clinical Evidence in Humans
Large-Scale Safety Studies
The most robust human evidence does not demonstrate increased thyroid cancer risk:
A comprehensive US commercially insured population study (2010-2014) found no significant elevated risk of thyroid cancer among liraglutide initiators after adjusting for latency effects, with relative risks ranging from 1.00 (95% CI 0.56-1.79) versus metformin. 3
This study revealed important surveillance bias: liraglutide cases had smaller thyroid nodules (67% were microcarcinomas ≤10mm versus 43% in comparators) and shorter time-to-diagnosis, suggesting increased medical surveillance rather than true increased cancer risk. 3
A 2012 meta-analysis found liraglutide was not associated with increased thyroid cancer risk (OR 1.54,95% CI 0.40-6.02). 4
Case Reports and Mechanistic Studies
A case report documented a woman with pre-existing MTC who showed no calcitonin elevation despite 6 months of dulaglutide 2.0 mg treatment, suggesting GLP-1 receptor agonists do not stimulate existing medullary thyroid tumors. 5
Laboratory research indicates liraglutide may actually inhibit thyroid cancer cell proliferation and migration through the PI3K/Akt/mTOR pathway in both medullary and papillary thyroid cancer cells. 6
Key Differences Between Rodents and Humans
The critical distinction is that rodents have substantially higher densities of GLP-1 receptors on thyroid C-cells compared to humans, explaining the species-specific tumor development. 5, 7 This fundamental biological difference undermines the applicability of rodent findings to human risk assessment.
Current Guideline Recommendations
Major diabetes guidelines acknowledge the rodent findings but do not restrict GLP-1 receptor agonist use based on thyroid cancer concerns in patients without contraindications:
The 2025 American Diabetes Association Standards of Care note that "thyroid C-cell tumors identified in rodents; human relevance not determined." 2
The 2022 ADA guidelines similarly state there is a "black box warning: Risk of thyroid C-cell tumors in rodents; human relevance not determined." 2
The 2018 ACC Expert Consensus lists personal/family history of MTC and MEN2 as absolute contraindications but does not recommend avoiding these agents in other patients. 2
Clinical Practice Implications
For patients WITHOUT contraindications: Victoza can be safely prescribed with appropriate counseling about the theoretical risk based on animal studies and symptoms to monitor. 2, 1
Screening recommendations: Routine calcitonin screening is not recommended before initiating GLP-1 receptor agonists, as the human relevance of rodent findings remains undetermined and population studies show no increased risk. 3, 7
If thyroid nodules are discovered: The increased detection of small thyroid nodules in liraglutide users likely represents surveillance bias rather than drug-induced pathology, particularly microcarcinomas detected shortly after drug initiation. 3