Semaglutide is a medication classified as a glucagon-like peptide-1 (GLP-1) receptor agonist, primarily approved for managing type 2 diabetes and assisting with long-term weight management. The medication works by mimicking a naturally occurring hormone that helps regulate appetite and blood sugar levels. Given its widespread use, questions often arise about its effects on other major organ systems, especially the thyroid gland, which controls metabolism throughout the body. The relationship between semaglutide and thyroid health has been a common focus of safety discussions for both new and existing users.
The Specific Connection to Thyroid C-Cell Tumors
The primary safety concern linking semaglutide to the thyroid gland originates from non-human studies involving rodents. In these animal studies, semaglutide and other GLP-1 receptor agonists were found to cause a dose-dependent increase in the incidence of thyroid C-cell tumors. These tumors are derived from the parafollicular C cells of the thyroid, which are responsible for producing the hormone calcitonin.
This finding led to the issuance of a Boxed Warning by the U.S. Food and Drug Administration (FDA), the agency’s most serious safety alert. The warning specifically highlights the risk of Medullary Thyroid Carcinoma (MTC), a rare form of thyroid cancer that develops from these C-cells. MTC accounts for a small percentage of all thyroid cancers, typically between 3% and 10%.
The relevance of these rodent findings to human physiology remains undetermined. Rodents have a significantly higher concentration of GLP-1 receptors on their thyroid C-cells compared to humans, suggesting a species-specific effect. Continuous activation of these receptors in rodents, as seen in the studies, led to C-cell proliferation and tumor formation.
Although human studies have not confirmed an increased risk of MTC with semaglutide use, the potential for a serious complication necessitates the warning. Postmarketing reports of MTC have occurred in patients using other GLP-1 receptor agonists, but the data are insufficient to establish a definitive causal relationship in humans. Therefore, the warning exists as a measure of caution for a potentially severe, though unproven, risk in people.
Semaglutide’s Impact on Existing Thyroid Conditions
Semaglutide does not appear to directly alter the levels of thyroid-stimulating hormone (TSH) or the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in a healthy person. However, the medication’s effect on the gastrointestinal system and subsequent weight loss can indirectly influence thyroid management for individuals already on treatment. Many patients with conditions like hypothyroidism, including Hashimoto’s disease, take a daily dose of synthetic thyroid hormone, such as levothyroxine.
Semaglutide works in part by delaying gastric emptying, which is the rate at which food moves from the stomach to the small intestine. This delayed movement can potentially affect the absorption rate of orally administered medications, including levothyroxine. One study involving oral semaglutide showed a 33% increase in total T4 exposure when co-administered with levothyroxine, indicating a possible change in how the body processes the medication.
Weight loss, regardless of the method, reduces the total body mass that needs to be supported by thyroid hormone. Since levothyroxine dosing is often calculated based on body weight, significant weight reduction achieved with semaglutide can mean the existing hormone replacement dose becomes too high. This can potentially lead to iatrogenic hyperthyroidism, where a patient experiences symptoms of an overactive thyroid due to medication overdose.
For patients with pre-existing thyroid conditions, routine monitoring of TSH levels is highly recommended. Healthcare providers may need to adjust the levothyroxine dose to prevent over-replacement and maintain optimal thyroid function, especially after significant weight loss. Patients should be consistent with the timing of their thyroid medication, often taking it on an empty stomach, to minimize absorption fluctuations.
Contraindications and Necessary Patient Screening
Semaglutide is expressly contraindicated for a specific group of patients due to the theoretical risk of MTC. Individuals with a personal history of MTC should not take the medication. Likewise, those with a family history of MTC are advised to avoid its use.
The drug is also contraindicated for people diagnosed with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). MEN 2 is a rare genetic disorder that significantly predisposes individuals to developing MTC, making semaglutide use inappropriate for this population. This condition is screened for as part of the necessary patient assessment before prescribing the drug.
Before prescribing semaglutide, doctors must conduct a thorough screening process that includes taking a detailed personal and family medical history. This history check specifically seeks to identify any past instances of MTC or the presence of MEN 2 syndrome. This screening is the main way healthcare providers mitigate the potential risks associated with the Boxed Warning.
Patients who are prescribed semaglutide must be fully informed about the potential signs of a thyroid tumor. They should be instructed to immediately report symptoms to their healthcare provider, including:
- The appearance of a lump or mass in the neck.
- Persistent hoarseness or changes in voice.
- Difficulty swallowing.
- Shortness of breath.