Skip to content

Ozempic and Thyroid Cancer

Share this article

Listen to this article on Spotify, or watch it on YouTube.

Ozempic and other GLP-1 agonists in the same class, like Wegovy, all seem to have similar black box warnings: “The risk of thyroid C-cell tumors”. If you’re taking one of these drugs or want to take it, you might be concerned about thyroid cancer.

But to really understand how real this risk is, we need to understand the evidence behind this warning. Let’s dive into the research behind these warnings for GLP-1 agonists, to determine just how real the risk is, and if you need to worry about this warning.

History of FDA cancer warnings

Exenatide was the first GLP-1 agonist approved by the FDA in 2005. Even from the beginning, its approval came with a warning on the label advising against using it in patients with certain conditions, such as medullary thyroid cancer or a family history of it. This initial warning was based on research done on animals.

You see, GLP-1 receptors, which these medications target, aren’t only found in the pancreas and gut. They’re also present in a type of thyroid cell called C cells, which release calcitonin into the body. These cells are involved in a specific type of thyroid cancer called medullary thyroid cancer.

Studies done on rodents showed that increasing doses of GLP-1 agonists over a certain period of time led to an increase in thyroid C-cell tumors, likely due to the overstimulation of these cells.

However, this relationship wasn’t observed in monkeys, and in humans, C cells are much less abundant and have lower levels of GLP-1 receptors, meaning that GLP-1 agonist drugs likely won’t stimulate these cells as strongly as in rodents.

One of the first studies that looked at humans searched into the FDA’s database of reported adverse events. The study uncovered a troubling fact: patients treated with exenatide, a GLP-1 agonist, were more likely to develop thyroid cancer.

But that wasn’t all. The research also showed a significant uptick in pancreatic cancer cases among the same group.

GLP-1 agonists and cancer

Evidence of no risk

Oddly enough, several subsequent studies since then have cast doubt on the initial findings regarding thyroid cancer risks.

For example, the LEADER trial looked at another GLP-1 agonist called liraglutide in patients with type 2 diabetes and found no evidence of C-cell cancers. And there was another meta-analysis in type 2 diabetic patients that also failed to find any significant correlation between liraglutide use and thyroid cancer.

Furthermore, additional studies comparing type 2 diabetes patients who took exenatide versus other antidiabetic drugs, found no significant association between exenatide use and an increased risk of thyroid cancer.

Evidence of risk

However, nearly all of these studies that show no link between GLP-1 agonists and thyroid cancer are funded directly by the companies that own these drugs.

Also, these studies don’t paint a complete picture, because they focus on older and weaker GLP-1 agonists, like exenatide or liraglutide.

The newer and stronger GLP-1 agonists, like semaglutide or tirzepatide, lack much statistical information for us to draw any conclusions from, simply because they haven’t been on the market for long enough.

One study that wasn’t funded by these drug companies found that thyroid cancer was reported more frequently in diabetics using GLP-1 agonists.

Interestingly, the study compared three different GLP-1 agonists: exenatide, liraglutide, and dulaglutide. Of the three, liraglutide (also known as Victoza or Saxenda) was the most strongly associated with thyroid cancer. This is concerning because liraglutide is also the strongest GLP-1 agonist of the three.

So, if a strong GLP-1 agonist like liraglutide is potentially more associated with thyroid cancer, what does that mean for even stronger GLP-1 agonists like Ozempic or Mounjaro? We just don’t know yet, because there isn’t enough data available, and much of the available data is quite old.

In fact, more recent evidence has suggested that there might be a link between these medications and thyroid problems.

A recent meta-analysis of 45 trials did find an increased risk for overall thyroid disorders, although no specific thyroid disorder stood out from the rest.

Another independent study found that GLP-1 agonists did increase the risk of thyroid cancers, although it seemed to decrease the risk of other types of cancer.

Also, in a recent study conducted by the French healthcare system, new data has emerged that suggests that patients with type 2 diabetes who take GLP-1 agonists may actually have a moderate risk of developing thyroid cancer. What’s more, this increase in risk was seen across all types of thyroid cancer in patients who used these medications for 1-3 years.

Summary of evidence

So although numerous studies have been conducted, there is still no conclusive evidence linking GLP-1 agonists to thyroid cancer in humans. However, there are some critical takeaways from the research:

  1. The safety studies that found no thyroid cancer risks only examined weaker GLP-1 agonists, which means there may be a different risk profile for the newer, stronger drugs.
  2. The studies tested smaller doses used in diabetes, which may not accurately reflect the much higher doses used for obesity treatment. Keep in mind that the use of GLP-1 agonists for obesity has only recently been approved.
  3. Many of these studies were funded by the drug companies themselves, which could introduce bias into the results.
  4. Many studies not funded by companies did find varying degrees of thyroid cancer risk associated with these drugs.

Overall, the evidence suggests that older and weaker GLP-1 agonists used for diabetes may slightly increase the risk of thyroid cancer, but this weak effect may not always be detected. This is likely because these drugs were not yet potent enough to reliably cause this problem.

However, when using drugs like Ozempic or Wegovy for weight loss, we are dealing with newer and stronger GLP-1 agonists, administered at much higher doses.

It would be a grave mistake to assume that the safety studies conducted on drugs approved over a decade ago still hold true for the newer ones.

Concealing the risks

In 2017, Novo Nordisk, the company that owns Victoza, a GLP-1 agonist, was fined $58 million USD for attempting to conceal the drug’s potential to increase the risk of medullary thyroid cancers.

The FDA had mandated that Novo Nordisk provide doctors with information about the drug’s risks through a Risk Evaluation and Mitigation Strategy (REMS).

Nevertheless, some of Novo Nordisk’s sales representatives provided doctors with false or misleading information, resulting in some physicians being unaware of the risks when prescribing the drug.

Although the FDA had required Novo Nordisk to modify the REMS to increase awareness, the company allegedly instructed its sales force to further obscure the risk information and misled physicians into thinking that the potential cancer risk associated with Victoza was not important.

Novo Nordisk also owns Ozempic and Wegovy, and these drugs have the potential to stimulate C cells in the thyroid significantly more than their older and weaker counterparts, like Victoza.

Will this lead to a significant increase in the risk of thyroid cancers? It seems very possible, but unfortunately until we have more information, we can’t know for sure. And let’s face it: Novo Nordisk has a lot to gain here by concealing any known increases in thyroid cancer risks from taking Ozempic or Wegovy.

Remember when they were fined $58 million by the FDA for concealing Victoza’s thyroid cancer risks? That same year, Victoza still raked in $3.4 billion USD. And now, with Ozempic sales reaching a whopping $8.6 billion USD in 2022, the stakes are higher than ever.

Overall summary

In the pursuit of shedding those extra pounds, the glitz and glam of these newer GLP-1 agonists like Ozempic and Mounjaro can blind us to their dark side.

The thyroid cancer risks associated with these GLP-1 agonists should not be taken lightly, and it’s high time we stop underestimating them.

You should always weigh the benefits against the risks and make an informed decision before jumping on the GLP-1 agonist bandwagon. After all, your health is worth more than just a number on the scale.

Learn more about

Citations

Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012;98(2):271-284. doi:10.1016/j.diabres.2012.09.008

Bezin J, Gouverneur A, Pénichon M, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. 2023;46(2):384-390. doi:10.2337/dc22-1148

Bjerre Knudsen L, Madsen LW, Andersen S, et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation [published correction appears in Endocrinology. 2012 Feb;153(2):1000. Moerch, Ulrik [added]]. Endocrinology. 2010;151(4):1473-1486. doi:10.1210/en.2009-1272

DOJ. Novo Nordisk Agrees to Pay $58 Million for Failure to Comply with FDA-Mandated Risk Program. https://www.justice.gov/opa/pr/novo-nordisk-agrees-pay-58-million-failure-comply-fda-mandated-risk-program Accessed Mar 19, 2023

Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011;141(1):150-156. doi:10.1053/j.gastro.2011.02.018

FiercePharma. Novo’s Victoza won’t face Teva copies until 2023. Can semaglutide fill the gap by then? https://www.fiercepharma.com/pharma/novo-nordisk-teva-ink-victoza-settlement-for-december-2023-generic-launch Accessed Mar 19, 2023

Hegedüs L, Sherman SI, Tuttle RM, et al. No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial. Diabetes Care. 2018;41(3):620-622. doi:10.2337/dc17-1956

Hu W, Song R, Cheng R, et al. Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2022;13:927859. Published 2022 Jul 11. doi:10.3389/fendo.2022.927859

Latif W, Lambrinos KJ, Rodriguez R. Compare And Contrast the Glucagon-like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2022 Mar 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151/

Liang C, Bertoia ML, Ding Y, et al. Exenatide use and incidence of pancreatic and thyroid cancer: A retrospective cohort study [published correction appears in Diabetes Obes Metab. 2020 Jun;22(6):1006]. Diabetes Obes Metab. 2019;21(4):1037-1042. doi:10.1111/dom.13597

Mali G, Ahuja V, Dubey K. Glucagon-like peptide-1 analogues and thyroid cancer: An analysis of cases reported in the European pharmacovigilance database. J Clin Pharm Ther. 2021;46(1):99-105. doi:10.1111/jcpt.13259

Ozempic. FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209637lbl.pdf Accessed Mar 19, 2023.

Rachel Pessah-Pollack. TikTok’s Fave Weight Loss Drugs: Link to Thyroid Cancer? – Medscape – Mar 15, 2023.

Rosol TJ. On-target effects of GLP-1 receptor agonists on thyroid C-cells in rats and mice. Toxicol Pathol. 2013;41(2):303-309. doi:10.1177/0192623312472402

Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021 Jul 7;12:645563. doi: 10.3389/fendo.2021.645563. Erratum in: Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. PMID: 34305810; PMCID: PMC8294388.

ThePharmLetter. Novo Nordisk’s sales rocket in 2022. https://www.thepharmaletter.com/article/novo-nordisk-s-sales-rocket-in-2022 Accessed Mar 19, 2023.

Wang J, Kim CH. Differential Risk of Cancer Associated with Glucagon-like Peptide-1 Receptor Agonists: Analysis of Real-world Databases. Endocr Res. 2022;47(1):18-25. doi:10.1080/07435800.2021.1955255

Wegovy. FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf Accessed Mar 19, 2023.

Yang Z, Lv Y, Yu M, et al. GLP-1 receptor agonist-associated tumor adverse events: A real-world study from 2004 to 2021 based on FAERS. Front Pharmacol. 2022;13:925377. Published 2022 Oct 25. doi:10.3389/fphar.2022.925377


See also

  • 3 Tips to BEST Use Rybelsus
    It’s more important than you might think to take Rybelsus with minimal water on an empty stomach and waiting at least 30 minutes before eating.
  • Comparing Weight Loss Drugs in 2024
    Ozempic and Mounjaro are highly effective at treating obesity, however there are many other approved and off-label options that also work.
  • Bupropion vs Contrave vs Naltrexone
    Contrave is a synergistic combination of buproprion and naltrexone, which can be replicated to some degree using the generics individually.
  • New Obesity Drugs in 2024
    New obesity drugs target more than just GLP-1 and do much more than suppress appetite for a more nuanced approach to weight loss.
  • Mounjaro: Who Loses the Most Weight?
    White or Asian younger women who use metformin and have lower sugar and lipid levels tend to experience more weight loss with Mounjaro.

Share this article

Leave a Reply

Your email address will not be published. Required fields are marked *