Thyroid cancer risks and medication timing with oral GLP-1s

Like most prescriptions, glucagon-like peptide 1 (GLP-1) medications to manage weight come with potential risks. One safety consideration that often stands out: Do not take this medication if you or a family member has had medullary thyroid carcinoma or if you have multiple endocrine neoplasia syndrome type 2.

If you have hypothyroidism, a thyroid nodule, or a history of thyroid cancer, that warning may seem alarming. However, it applies to a specific thyroid cancer called medullary thyroid carcinoma (MTC) and a rare inherited condition called multiple endocrine neoplasia syndrome type 2 (MEN2). Hypothyroidism, hyperthyroidism, goiter, thyroid nodules, and other forms of thyroid cancer, by themselves, should not prevent someone from taking a GLP-1 medication.

However, if you take a thyroid hormone replacement medication, such as levothyroxine, you may need to change your daily routine if you start taking an oral, pill form of GLP-1 such as Wegovy or Foundayo to ensure both work effectively.

Let's answer some common questions about GLP-1s and thyroid cancer and ways to optimize your medication schedule.

Why do GLP-1 medications carry a thyroid cancer warning?

Potential risks with medullary thyroid carcinoma

MTC begins in the C cells of the thyroid gland. These are different from thyroid follicular cells, which produce thyroid hormone and give rise to more common thyroid cancers.

In studies involving rodent models, researchers found that some GLP-1 medications caused C cells to grow and become more active. Over time, some animals developed tumors.

Human thyroid tissue does not necessarily respond the same way, and so far, human studies have been reassuring. A large Scandinavian study found no substantial increase in thyroid cancer among patients taking GLP-1 receptor agonists over an average follow-up of nearly four years. Other large studies have reached similar conclusions.

However, MTC is rare – studies involving hundreds of thousands of patients may include too few cases to exclude long-term risk. Because of that uncertainty, the Food and Drug Administration advises against these weight-management medications for people at elevated risk of MTC.

Potential risks with MEN2

Multiple endocrine neoplasia syndrome type 2 is a rare hereditary cancer syndrome caused by a change in the RET gene, which is involved with cell growth – including thyroid C cells.

About 95% of people with MEN2A, the most common subtype of the disease, screen positive for MTC. MEN2 can also increase the risk of tumors of the adrenal glands and hyperparathyroidism, in which the parathyroid glands produce too much hormone.

Because GLP-1 medications have been linked to C-cell growth in animal studies, people with a personal or family history of MEN2 or a known RET mutation should not take GLP-1s. There is no need to get tested for a RET mutation prior to starting a GLP-1 medication if there is no personal or family history of MTC or MEN2.

What about other thyroid conditions?

Most thyroid cancers are not MTC. Papillary, follicular, and Hürthle cell thyroid cancers arise from a different kind of thyroid cell and do not carry the same concerns related to GLP-1 medications.

The same is true for several common thyroid conditions, including:

• Goiter or multinodular goiter
• Graves' disease and other causes of hyperthyroidism
• Hashimoto's disease and other causes of hypothyroidism
• Thyroid nodules

If you have one of these other thyroid conditions besides MTC or MEN2, be sure to mention it to your doctor before starting a GLP-1. You and your doctor should consider your medical history, the potential benefits of treatment, other medications, and possible side effects before deciding whether a GLP-1 medication is right for you.

What role does the thyroid play in weight gain?

Thyroid hormones help regulate how the body uses energy, so thyroid disease can affect weight. Hyperthyroidism often causes weight loss. Untreated or undertreated hypothyroidism can contribute to some slight weight gain. Approximately five to 10 pounds may be related to hypothyroidism, often from retaining salt and water rather than accumulating body fat.

Once thyroid hormone levels are back in the normal range, a person's ability to gain or lose weight is generally similar to that of someone without a thyroid condition.

How should I take an oral GLP-1 with levothyroxine?

The answer depends on which oral GLP-1 medication you take. Weekly injectable medications should be taken in the morning, and you can take your thyroid replacement medication at the same time if you wish.

The new once-daily Wegovy tablets, however, must be taken in the morning on an empty stomach with up to 4 ounces of plain water and no other medications. Then, wait 30 minutes before taking other medications or eating or drinking beverages other than water.

The new once-daily Foundayo (orforglipron) tablets can be taken at the same time as other medications.

Levothyroxine, the most common medication for hypothyroidism, should also be taken on an empty stomach because food, supplements, and certain medications can change how much the body absorbs. Levothyroxine should not be taken at the same time as either oral Wegovy or Foundayo.

For patients taking both oral Wegovy and levothyroxine, I generally recommend:

1. Take the GLP-1 tablet immediately after waking with up to 4 ounces of water.
2. Wait at least 30 minutes.
3. Take levothyroxine.
4. Wait at least another 30 minutes before eating breakfast.
5. Take other medications as directed by your doctor or pharmacist.

For patients taking both Foundayo and levothyroxine, I generally recommend:

1. Take levothyroxine immediately after waking.
2. Wait at least 30 minutes before eating breakfast.
3. Take Foudayo together with other medications as directed by your doctor or pharmacist.

Talk with your doctor about when you should take your medications and get regular blood draws to check your thyroid hormone levels.

Should my thyroid medication change if I'm taking a GLP-1?

Because levothyroxine dosing is influenced in part by body weight, significant weight changes can change how much medication you need. I usually advise patients to talk with their doctor after losing or gaining 10-20 pounds.

You may need testing sooner if thyroid symptoms develop.

Possible signs that you are not getting enough thyroid hormone can include:

• Constipation
• Difficulty concentrating or "brain fog"
• Dry skin or hair
• Depressed mood
• Fatigue
• Feeling unusually cold

Possible signs that you are getting too much thyroid hormone include:

• Anxiety or irritability
• Unusually hot or sweaty feeling
• Racing heart or palpitations
• Shaky hands
• Trouble sleeping

These symptoms can have many causes: Experiencing any of them does not necessarily mean your levothyroxine dose is wrong. A blood test can show whether your level of thyroid hormones is in the desired range.

Questions to ask your doctor

Knowing the exact name and history of your thyroid condition is one of the most useful steps you can take. Consider asking your doctor:

• What type of thyroid disease or thyroid cancer did I have?
• Does my personal or family history include medullary thyroid cancer or MEN2?
• Do I need genetic testing for MEN2 or a RET mutation?
• Do I have a thyroid nodule that should be examined?

You can also better understand your treatment options by also asking:

• How should I schedule my GLP-1 and other medications?
• How much weight loss should prompt another test of my thyroid hormone levels?
• Which symptoms should prompt me to call before my next planned appointment?

For most people with common thyroid conditions, a thyroid diagnosis alone does not rule out GLP-1 treatment. The most important step is understanding which thyroid condition you have and discussing your medical history with your doctor before starting a new medication.

If a GLP-1 medication is not recommended for your condition or if you prefer not to take one, ask about other ways to manage your weight or your diabetes. Depending on your health and your goals, weight management treatment options may also include other medications, nutrition and activity support, an endobariatric procedure, or bariatric surgery.