GLP-1 Receptor Agonists (Weight Loss Drugs) vs. Thyroid Cancer Risk: Should You Worry About Semaglutide & Tirzepatide? (2025)

Do GLP-1 receptor agonist weight loss drugs like semaglutide and tirzepatide increase risk of thyroid cancers?

Concerns about potential cancer risks associated with GLP-1 RAs (glucagon-like peptide-1 receptor agonists), drugs routinely used for diabetes and obesity treatment, primarily stem from a combination of rodent studies and human observational data.

Rodent studies test extremely high doses (~8-60x the human therapeutic levels) and found that rats and mice experienced: thyroid C-cell hyperplasia, increased calcitonin secretion, and developed: C-cell adenomas or medullary thyroid carcinomas (MTC).

How does this happen? Rodents are known for having a high density of GLP-1 receptors in thyroid C cells – making them highly-sensitive to GLP-1 RA stimulation (this receptor density is not mirrored in humans or nonhuman primates).

GLP-1 Receptor Agonist Thyroid Cancer Mechanism Chain

The mechanisms for GLP-1 RA-induced cancer in rodents specifically is thought to go something along the lines of:

1. Activate GLP-1 receptors in the thyroid: Thyroid parafollicular C cells express a high density of GLP-1 receptors. When GLP-1 RA drugs bind to these receptors, they activate a signaling cascade that increases cAMP (cyclic AMP).

2. cAMP-dependent signaling: The increase in cAMP triggers downstream signaling pathways including activation of PKA (protein kinase A).

3. Calcitonin secretion: The cAMP-PKA activation leads to increased secretion of calcitonin (a hormone produced by C cells) and increased calcitonin gene expression.

4. C-cell hyperplasia: The combination of calcitonin secretion and increased calcitonin gene expression leads to C-cell hyperplasia (increased cell production).

5. Tumor formation: Downstream of the hyperplasia comes tumor formation. Prolonged GLP-1RA treatment causes C-cell adenomas and medullary thyroid cancers as a result of the calcitonin-induced hyperplasic state.

6. mTOR pathway: GLP-1 RA drugs may also stimulation mTOR (mammalian target of rapamycin) via cAMP signaling. This can increase phosphorylation of ribosomal S6 protein and promote cell growth.

In humans, there are some observational data (from epidemiological studies) suggesting that GLP-1 RA drugs may increase risk of certain cancers – primarily, thyroid cancer (just like the rodents).

Risk is thought to be profoundly reduced in humans (relative to rodents) because we use much lower relative doses than the rodents were exposed to in research AND because we have much lower density of thyroid C cells.

• Rodents: Thyroid C cells make up ~4-10% of thyroid epithelial mass.

• Humans: Thyroid C cells make up less than 0.1% of thyroid epithelial mass.

So while this doesn’t mean GLP-1 RA drugs can’t cause thyroid cancers in humans, it means the odds are significantly lower in humans as a result of both: lower dosing AND lower thyroid C cell density.

If we do a simplistic analysis estimating the risk reduction from humans using lower doses and having lower thyroid C cells, my math yields an estimated ~1000-fold risk reduction.

How did I get this estimate?

• Rodents have ~50x more thyroid C cells per unit of thyroid tissue vs. humans

• Rodents are exposed to ~20-60x higher doses vs. humans

If I assume cancer risk is directly proportional to both C cell density and dose, the relative risk in humans compared to rodents would be reduced by a factor of 1000 (C cell ratio * Dose ratio = 50 x 20 = 1000). Yields a theoretical ~1000-fold risk reduction.

This is just an imprecise estimation that may be highly flawed… but is one way to think about thyroid cancer risk from drugs like semaglutide.

Anyways, to make people aware of the risk (given what was found in rodent research), the FDA issued a “Black Box Warning” for all GLP-1 RA drugs (semaglutide, tirzepatide, et al.)… they want to make people aware of the potential risk here.

What does the real-world observational data indicate so far? Risk of thyroid cancer (and other cancers) remains extremely low, but perhaps slightly higher than not using a GLP-1 RA.

Overall cancer risk might even decrease because GLP-1 RAs are linked to lower risk of developing other types of cancers. Remember: obesity significantly increases risk of many cancers. Thus treating obesity reduces risk of many other cancers.

The net effect for most obese people is still favorable and taking on any potentially increased thyroid cancer risk would be a logical, smart gamble because you address early risk of obesity-related death and reduce risk of other cancers.

What do I think about GLP-1 drugs (semaglutide & tirzepatide) & thyroid cancer risk?

It is a legitimate concern. I think these are extremely useful drugs for obesity, diabetes, metabolic syndrome, etc. but a majority of people haven’t been using highly-potent GLP-1 RAs like semaglutide until recently (circa 2020-2025).

Humans still have thyroid C cells: Sure we have a smaller number than rodents. But this means GLP-1 RA drugs can still interact with them to modulate cAMP/PKA, calcitonin, etc. Since there are lower numbers, risk of hyperplasia is reduced relative to rodents. However, even small numbers of cells can mutate. We are not immune.

The more total time exposure and the higher the concentration/dose – the higher one’s odds become (in my estimation).

Thyroid cancer doesn’t develop overnight: The timeline for thyroid cancer can be variable. Progression from initial cellular changes to a tumor that’s large enough to be clinically detected can span years or decades (10-20 years).

• Human thyroid C cells normally divide very slowly… even if a GLP-1 agonist increased their proliferation rate, this “boost” might shorten the doubling time somewhat - but not from years down to months.

• A generous assumption (assuming it decreases doubling time from 2 years to 1 year) would mean it takes ~10-20 years for a cell clone to accumulate enough divisions to form a tumor that reaches clinical detectability.

• Genetics and other environmental factors could potentially accelerate this timeline in a subset of users.

So the main reason I don’t think the cancer risk should be overlooked with GLP-1 drugs is because we don’t have people who’ve been on these drugs long enough for a critical mass (#) of cancer cases to emerge.

The GLP-1 drug Byetta (exenatide) has been approved since 2005, but it is 5-10x less potent than semaglutide (meaning GLP-1 receptor impact isn’t as substantial)… and we are just coming up on the ~20 year marker.

Liraglutide (Victoza & Saxenda) was approved for T2DM in various formats in 2010 and again in 2014 – as was albiglutide (Tanzeum) and dulaglutide (Trulicity). Most of these are far less potent (2-10x less) than semaglutide and tirzepatide.

I guess by year ~2050 we’ll know if there’s a sudden flood of thyroid cancers among GLP-1 or former GLP-1 users… probably the medications.

A flood is unlikely though… it would be more like an increased rate relative to non-GLP-1 drug users… may not be too insane, but lawsuits may result.

An optimistic mind might suspect that by 2050 we’ll already have a cure for most cancers due to the advancement of AI/medical breakthroughs OR some alternative that has completely usurped GLP-1s as the mainstream weight loss intervention.

GLP-1 Drugs & [Thyroid] Cancer (Research)

It should be noted that there are “limitations” associated with all of these studies. You can examine each one and determine how each may be limited, but try not to dismiss any particular study outright based only on the limitations because you don’t like the data.