Semaglutide Thyroid Cancer Warning: What It Means

Semaglutide medications carry a boxed warning about thyroid cancer on their labels. More specifically, the FDA label states that these medications may lead to thyroid C-cell tumors.

To fully understand what this warning means, the clinical evidence behind it, and who should consider alternatives due to an increased risk of medullary thyroid carcinoma, let's take a closer look.

Why Semaglutide Has a Thyroid Warning

Semaglutide is a medication that mimics the effects of GLP-1, a naturally occurring hormone that plays a role in digestion, appetite, and blood sugar regulation. In animal studies, semaglutide has been associated with the development of thyroid C-cell tumors in rodents, though findings in animal studies don't always translate to humans.

Few clinical trials with human participants specifically look at if semaglutide causes thyroid C-cell tumors. The evidence we have doesn't support that the risk is the same in people as in rodents. A 2024 review of the literature is one of the most comprehensive papers on the topic. Using data from ten randomized control trials with a total of 14,550 participants, the review's authors reported that the thyroid cancer incidence was less than 1%, which is not higher than the general population (although this cannot rule out small increases in cancer risk).

Those animal study findings are what prompted the boxed warning on Ozempic, Wegovy, and Rybelsus. Boxed warnings are reserved for problems that may result in death or serious health problems. The FDA states it is currently unknown whether these findings are applicable to humans.

Still, more evidence is required. For now, these medications are not recommended for those who are at a higher risk of medullary thyroid carcinoma. This includes people with a family history of this cancer type, as well as individuals with Multiple Endocrine Neoplasia syndrome type 2 (MEN2).

What Is Medullary Thyroid Carcinoma?

Thyroid cancer occurs when cancer begins in cells located in the thyroid, a butterfly-shaped gland in the throat. There are four main types of thyroid cancer, but semaglutide is associated with only one type in animal studies: medullary thyroid carcinoma. This type of thyroid cancer is the rarest, making up 3-4% of all thyroid cancer cases.

Inside the thyroid, there are parafollicular C cells, nicknamed C-cells. These produce and send out calcitonin, which is important for calcium homeostasis, an essential process for bone health and nerve function. If these C-cells become cancerous and grow out of control, someone is diagnosed with medullary thyroid carcinoma.

Because of the c-cell tumor growth found in animal studies, it’s possible that semaglutide increases the risk of medullary thyroid carcinoma. As such, semaglutide is not recommended for those with a family history of this cancer type.

What Is MEN2?

Multiple Endocrine Neoplasia syndrome type 2 (MEN2) is a hereditary syndrome caused by a mutation in the RET gene. It predisposes affected individuals to tumors of the thyroid (medullary thyroid carcinoma), adrenal glands (pheochromocytoma), and parathyroid glands. This increases the risk of tumors in the thyroid gland, adrenal glands, and parathyroid gland. This condition has a strong genetic component, meaning someone is significantly more likely to have MEN2 if their parents or other close family members do.

One of the risks associated with MEN2 is that of C-cell tumor growth. Because of the heightened likelihood for these tumors, semaglutide is not recommended for people with MEN

Who Should Not Use Semaglutide According to Labeling?

According to the labeling, semaglutide is contraindicated (meaning not suitable) for people with:

• A personal or family history of medullary thyroid carcinoma: 25% of medullary thyroid carcinoma cancer cases run in families, and the condition appears to have a genetic component.
• MEN2: People with MEN2 are already at a higher risk of medullary thyroid carcinoma, so it’s not recommended to take a medication that may increase this risk further.
• Previous hypersensitivity to another semaglutide-type medication: This one isn’t related to thyroid cancer specifically, but it is an important contraindication listed on the FDA labels for such medications.

Even if you don’t fall into these groups, discuss any risks and whether a semaglutide-based medication is appropriate for you with a healthcare provider. They can assess your personal risk level and answer any questions about possible side effects.

Symptoms Patients Should Ask About

If taking semaglutide, the prescribing healthcare provider may offer regular check-ins to monitor progress, note any side effects, and assess the risk level for known safety concerns, including medullary thyroid cancer.

Still, if someone experiences any common symptoms of this cancer type, they should report them to a healthcare provider, either during these check-ins or between them. This allows the provider to fully consider symptoms and recommend appropriate next steps.

Neck Lump or Swelling

One of the first and most common signs of any type of thyroid cancer is a lump or swelling in the neck. This may appear in the early stages of the cancer, which often has few other symptoms. A doctor may feel for any lumps or swelling in the neck during annual exams, though you may also feel for this at home.

Trouble Swallowing

As medullary thyroid carcinoma spreads, it may result in trouble swallowing. Some people also report that they have pain when swallowing, not just that it’s difficult to do so.

Hoarseness

Since the thyroid sits in the throat, this type of thyroid cancer may affect nearby vocal cords and nerves associated with voice. Due to this proximity, hoarseness and changes in voice may be symptoms.

Shortness of Breath

As the cancer advances, another potential side effect is shortness of breath. This could range from struggling to breathe during a brisk walk to difficulty inhaling and exhaling deeply, even when sitting still.

Questions to Ask Before Starting Treatment

Before starting semaglutide (or any prescription medication for that matter), ask the prescribing healthcare provider a few questions so you understand the risk level and what to do if you experience any concerning symptoms or side effects.

Questions to ask during this conversation may include:

• Do I have any contraindications for this medication?
• Does my family history indicate this drug might not be a good fit?
• What symptoms should I report to you? What is the best way to report them?
• Are there alternatives if semaglutide is not appropriate?

Bottom Line

The boxed warning on semaglutide medications is rooted in animal study findings, not confirmed human evidence. Current data from large-scale clinical trials shows a thyroid cancer incidence of less than 1%, which is consistent with the general population.

For most people, this warning is informational. For those with a personal or family history of medullary thyroid carcinoma, or with MEN2, a healthcare provider will assess whether this medication is appropriate.

If you have any concerns about your personal risk level, speak with your healthcare provider before starting treatment.