PeptideJournal
Research13 min read

GLP-1 Agonists & Cancer Risk: Research Review

When millions of people start taking a new class of medication, one of the first questions that comes up — and should come up — is whether these drugs cause cancer.

When millions of people start taking a new class of medication, one of the first questions that comes up — and should come up — is whether these drugs cause cancer. For GLP-1 receptor agonists like semaglutide (Ozempic, Wegovy), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro), this question has been there since the beginning.

Rodent studies showed thyroid tumors. The FDA put a black box warning on these drugs. Patients worried. And now, after years of accumulating data from clinical trials, patient registries, and epidemiological studies involving millions of people, we can start to separate what the evidence actually shows from what the fears suggested.

The short version: the picture is more reassuring than alarming — but more complicated than a simple "yes" or "no."

Table of Contents

The Thyroid Concern: Where It Started {#the-thyroid-concern-where-it-started}

Before GLP-1 receptor agonists could be prescribed to humans, they had to go through animal testing. In rodent studies, these drugs caused C-cell hyperplasia, thyroid adenomas, and medullary thyroid carcinoma (MTC) in a dose-dependent and duration-dependent manner. More drug, longer exposure, more tumors.

This finding is the reason every GLP-1 receptor agonist — including semaglutide, liraglutide, exenatide, and dulaglutide — carries an FDA contraindication in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN2). It's the black box warning that patients often ask about.

But here's where the story gets more nuanced: European regulators looked at the same rodent data and came to a different conclusion. The European Medicines Agency (EMA) does not have similar contraindications or warnings in product information. Instead, they monitor the potential risk through routine pharmacovigilance.

Why the difference? Because there are important biological differences between rodent and human thyroid C-cells — and whether the rodent findings translate to humans has been a subject of debate since day one.

What Rodent Studies Found (and Why It Matters Less Than You Think) {#what-rodent-studies-found}

Thyroid C-cells produce calcitonin, a hormone involved in calcium regulation. In rodents, these cells express high levels of GLP-1 receptors. When you give rodents a GLP-1 agonist, the drug stimulates these C-cells, causing them to grow (hyperplasia) and, with prolonged exposure, develop into tumors.

The issue: human thyroid C-cells express far fewer GLP-1 receptors than rodent C-cells. Multiple studies have confirmed that GLP-1 receptor agonists don't cause clinically meaningful calcitonin elevation in humans — which is what you'd expect to see if the drugs were stimulating C-cell growth the way they do in rats and mice.

This doesn't mean the concern was invalid. It means the rodent model may not accurately predict what happens in humans. And determining what actually happens in humans requires large-scale, long-term human data — which we now have.

Human Data on Thyroid Cancer Risk {#human-data-on-thyroid-cancer-risk}

The Largest Studies Are Reassuring

International multisite cohort study (2025) — This study, published in Thyroid (2025), pooled data from six population-based databases across Canada, Denmark, Norway, South Korea, Sweden, and Taiwan. It compared 98,147 GLP-1 receptor agonist users with 2,488,303 DPP-4 inhibitor users (a different class of diabetes medication). The result: no increased risk of thyroid cancer with GLP-1 agonist use (pooled HR 0.81, 95% CI 0.59-1.12). No increased risk was observed even with higher cumulative doses. Follow-up ranged from 1.8 to 3.0 years.

Novo Nordisk comprehensive analysis (2025) — Published in Diabetes, Obesity and Metabolism (2026), this analysis reviewed all completed Novo Nordisk phase 2 and 3 trials of liraglutide and semaglutide conducted between 2006 and 2024. It covered 101,732 participants with 207,045 patient-years of exposure. Thyroid cancer rates were low across the board: 0.08% with GLP-1 agonists, 0.06% with placebo, and 0.03% with active comparators. Postmarketing surveillance showed an even lower rate of 0.001 cases per 100 patient-years. The analysis found no association between liraglutide or semaglutide use and thyroid cancer.

Retrospective cohort study (2025) — Published in Diabetes Care (2025), this study used propensity score matching and found no significant difference in thyroid cancer risk between patients treated with GLP-1 receptor agonists vs. SGLT2 inhibitors (HR 0.87; 95% CI 0.58-1.29).

One Study Raised a Different Signal

French case-control study (Bezin et al.) — This earlier nested case-control study reported a 46% increased risk of thyroid carcinoma with current GLP-1 receptor agonist use and a 58% increased risk with 1-3 years of cumulative use. However, this study has been heavily critiqued for methodological limitations, including potential confounding by indication and surveillance bias (patients on GLP-1 agonists may receive more thyroid screening) (Thyroid, 2025).

Meta-Analysis of Randomized Trials

A 2025 meta-analysis of randomized controlled trials published in Diabetes, Obesity and Metabolism looked specifically at cancer incidence across GLP-1 agonist trials. The overall picture: no significant increase in overall cancer risk from GLP-1 receptor agonist treatment. Liraglutide trials did show a numerically higher signal (odds ratio 2.82 for overall neoplasms), though this didn't reach statistical significance after adjustment. Semaglutide trials showed mixed results across individual studies.

The Pancreatic Cancer Question {#the-pancreatic-cancer-question}

GLP-1 receptors are found in pancreatic islets, acini, and ducts. Basic research has shown that GLP-1 therapy can promote acinar and duct cell proliferation. A 2011 report flagged an increased risk of pancreatitis and pancreatic cancer in patients on incretin therapy, which led to an FDA safety warning.

Complicating matters: type 2 diabetes itself is a known risk factor for pancreatic cancer. Separating the drug's effect from the disease's effect is a genuine challenge.

What the data shows

Meta-analyses are mostly reassuring. A 2025 systematic review in Endocrinology, Diabetes & Metabolism found that GLP-1 receptor agonists carry a slightly increased risk of acute pancreatitis, but the overall risk for pancreatic cancer was not elevated. A prior meta-analysis of seven cardiovascular outcome trials covering 56,004 patients found no significant difference in pancreatic cancer rates (OR 1.12, p = 0.56).

Population-based studies are negative. A 2024 cohort study following 543,595 patients over 7+ years found no increased pancreatic cancer risk (OR 0.50, 95% CI 0.15-1.71). A large analysis of over 38 million individuals with T2D found no association between GLP-1 agonist use and pancreatic cancer compared to other diabetes drugs (Diabetes & Metabolism Journal, 2024).

The FDA adverse event database flags a signal. An analysis of the FDA Adverse Event Reporting System (FAERS) from 2004-2020 found a significantly elevated proportional reporting ratio (9.86) for pancreatic cancer with GLP-1 agonists. However, FAERS data is subject to significant reporting biases — patients and doctors are more likely to report adverse events they're watching for, and the FDA warning itself likely increased reporting.

Current consensus: No convincing evidence that GLP-1 agonists cause pancreatic cancer, but the duration of follow-up in most studies is still relatively short (typically under 5 years). Longer-term data is needed.

The SELECT Trial: Cancer as a Secondary Outcome {#the-select-trial-cancer-as-a-secondary-outcome}

The SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) is the largest completed trial of high-dose semaglutide (2.4 mg weekly). Published in the New England Journal of Medicine (2023), it enrolled 17,604 adults with cardiovascular disease and obesity but without diabetes, following them for a mean of 40 months.

While the trial was designed to measure cardiovascular outcomes (it showed a 20% reduction in major adverse cardiovascular events), cancer was tracked as a safety outcome.

The key finding: cancer rates were not elevated with semaglutide. Serious adverse events related to cancers were not more frequent with semaglutide than with placebo. Gallbladder-related disorders were slightly more common, but cancer, acute kidney failure, and acute pancreatitis occurred at similar rates in both groups.

The limitation: the SELECT trial ran for about 3.3 years — long enough to detect clear safety signals but potentially too short to detect cancers that take years to develop. As the researchers noted, the relatively short duration "makes it infeasible to assess outcomes that require a longer time to develop, such as cancer."

The Obesity Connection: Could GLP-1 Agonists Reduce Cancer Risk? {#the-obesity-connection}

Here's where the cancer story takes an unexpected turn. Obesity is causally linked to at least 13 cancer types, according to the International Agency for Research on Cancer (IARC). These include cancers of the colon and rectum, liver, pancreas, kidney, endometrium, ovary, esophagus, stomach, gallbladder, post-menopausal breast, thyroid, multiple myeloma, and meningioma.

GLP-1 agonists cause substantial weight loss — semaglutide 2.4 mg produces roughly 15% weight loss in people with obesity. Tirzepatide produces even more. If obesity drives cancer, and these drugs reduce obesity, could they reduce cancer risk?

The hypothesis is plausible. But determining whether it's true requires understanding whether the cancer risk reduction from weight loss occurs on the timeline of months (unlikely for most cancers) or years to decades (more biologically plausible), and whether GLP-1 agonists might have direct anti-cancer effects independent of weight loss.

Preclinical research suggests several potential anti-tumor mechanisms of GLP-1 receptor activation, including anti-inflammatory effects, improved metabolic regulation, and effects on cell proliferation pathways. But these laboratory findings are far from proving cancer prevention in humans (PMC, 2025).

Cancer Risk Reduction Data from Large Studies {#cancer-risk-reduction-data-from-large-studies}

Several large observational studies have now reported associations between GLP-1 agonist use and reduced cancer risk:

Study 1: 1.6 Million Patients with T2D (JAMA Network Open, 2024)

This Case Western Reserve study followed 1,651,452 patients with type 2 diabetes and found that GLP-1 agonist use (compared to insulin) was associated with significantly reduced risk for 10 of 13 obesity-associated cancers, including esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Notably, GLP-1 agonists were not associated with reduced risk of post-menopausal breast cancer or thyroid cancer.

Study 2: 86,632 Matched Adults with Obesity (JAMA Oncology, 2025)

This study used a target trial emulation design with electronic health records from the OneFlorida+ network (JAMA Oncology, 2025). Overall cancer incidence was lower among GLP-1 agonist users vs. non-users (13.6 vs. 16.4 per 1,000 person-years; HR 0.83, 95% CI 0.76-0.91). Specific reductions were seen for endometrial cancer (HR 0.75), ovarian cancer (HR 0.53), and meningioma (HR 0.69). However, a possible increased risk of kidney cancer was flagged (HR 1.38).

Study 3: 170,000+ Patients (2025 ASCO Annual Meeting)

Presented at the American Society of Clinical Oncology annual meeting, this study of patients with diabetes and obesity found a 7% lower risk of obesity-related cancer and 8% lower risk of death from any cause with GLP-1 agonists vs. DPP-4 inhibitors. The benefit was stronger in women (8% cancer risk reduction, 20% lower mortality) and for colorectal cancers (16% fewer colon cancers, 28% fewer rectal cancers).

ASCO President Robin T. Zon called the findings "intriguing" but emphasized: "This trial does not establish causation. It hints that these drugs might have a preventative effect."

What these studies don't tell us

All of these studies are observational. They can't prove that GLP-1 agonists caused the cancer risk reductions. Possible confounders include:

  • Healthy user bias — People who take GLP-1 agonists may be more engaged with their healthcare overall
  • Surveillance bias — Users may receive different screening patterns
  • Confounding by BMI — Even after statistical adjustment, residual confounding by obesity severity is possible
  • Time window — Most follow-up periods are under 5 years, which may be too short for meaningful cancer prevention effects

Putting the Risks in Context {#putting-the-risks-in-context}

For patients trying to make sense of the data, here's a practical framework:

Thyroid cancer: Low concern for most patients

The largest and most recent human studies — including one covering over 2.5 million patients and another analyzing over 100,000 trial participants — found no increased thyroid cancer risk. The rodent findings don't appear to translate to humans at clinical doses. The exception: patients with a personal or family history of medullary thyroid cancer or MEN2 should not take GLP-1 agonists, per the FDA label.

Pancreatic cancer: Low concern, but worth monitoring

Multiple meta-analyses and large cohort studies show no significant increase. The slightly elevated pancreatitis risk is worth discussing with your doctor, especially if you have a history of pancreatic issues.

Overall cancer risk: No increase; possible decrease

The SELECT trial found no elevated cancer rates. Multiple observational studies suggest potential reductions in obesity-associated cancers. But these findings need to be confirmed with longer follow-up and, ideally, randomized trials designed to measure cancer outcomes.

Perhaps the most important context: obesity itself is a well-established cause of cancer. If GLP-1 agonists reduce obesity — and they do — the net effect on lifetime cancer risk may well be favorable, even before accounting for any direct anti-cancer properties. For patients choosing between remaining obese and taking a GLP-1 agonist, the cancer-risk math likely favors treatment.

FAQ {#faq}

Do GLP-1 agonists cause thyroid cancer?

The best available human evidence says no. Rodent studies showed thyroid C-cell tumors, but human thyroid cells have far fewer GLP-1 receptors. The largest human studies — covering millions of patients — have found no increased risk. That said, patients with a personal or family history of medullary thyroid cancer should not take GLP-1 agonists per the FDA label.

Should I get thyroid screening while on semaglutide?

The standard medical guidance does not recommend additional thyroid screening specifically because of GLP-1 agonist use in patients without risk factors for MTC. However, if you develop symptoms like a neck lump, persistent hoarseness, difficulty swallowing, or shortness of breath, see your doctor. Regular check-ups that include neck examination are reasonable.

What about pancreatic cancer risk?

Large meta-analyses and cohort studies have not found a significant increase in pancreatic cancer risk with GLP-1 agonist use. There is a small increased risk of acute pancreatitis. Patients with a history of pancreatitis should discuss risks with their prescriber. It's also worth noting that type 2 diabetes itself raises pancreatic cancer risk, making it difficult to separate drug effects from disease effects.

Could GLP-1 agonists actually prevent cancer?

Multiple large observational studies have found associations between GLP-1 agonist use and lower rates of several obesity-associated cancers, including colorectal, endometrial, and ovarian cancers. The mechanism may be weight loss, direct anti-cancer effects, or both. But these are observational findings — they can't prove causation. Randomized trials with cancer endpoints would be needed to confirm a preventive effect, and those would take many years to complete.

How do European and American regulators differ on the thyroid concern?

The FDA requires a black box warning and contraindication for patients with MTC history or MEN2. European regulators (EMA) do not have equivalent warnings, instead monitoring the risk through pharmacovigilance. This reflects different interpretations of the same rodent data and its relevance to humans.

What did the SELECT trial show about cancer?

The SELECT trial of semaglutide 2.4 mg in 17,604 patients with obesity and cardiovascular disease found no increased cancer rates with semaglutide compared to placebo over a mean follow-up of about 3.3 years. Cancer, acute kidney failure, and acute pancreatitis occurred at similar rates in both groups.

The Bottom Line {#the-bottom-line}

After more than a decade of GLP-1 agonist use and studies covering millions of patients, the cancer safety profile looks more reassuring than the early rodent data suggested.

Thyroid cancer risk in humans? The largest studies say no increased risk. Pancreatic cancer? No convincing signal. Overall cancer? No increase in clinical trials, and potentially a decrease based on observational data — especially for obesity-linked cancers.

The open question isn't really about GLP-1 agonists causing cancer. It's about whether their ability to reduce obesity could translate into meaningful cancer prevention over time. That question will take years to answer definitively.

For now, patients can take some reassurance: the drugs appear safe from a cancer perspective at the population level. Patients with medullary thyroid cancer history should avoid them per the label. Everyone else should discuss their individual risk factors with their doctor — but the cancer question, based on current evidence, shouldn't be the primary concern driving treatment decisions.

References {#references}

  1. Toro-Tobon D, Singh Ospina N, Brito JP. Thyroid cancer risk with GLP-1 receptor agonists: evidence, knowledge gaps, and the path forward. Thyroid. 2025. Link

  2. Glucagon-like peptide 1 receptor agonists and risk of thyroid cancer: an international multisite cohort study. Thyroid/PubMed. 2025. Link

  3. Assessment of thyroid cancer risk associated with glucagon-like peptide 1 receptor agonist use. Diabetes, Obesity and Metabolism. 2026. Link

  4. Risk of thyroid tumors with GLP-1 receptor agonists: a retrospective cohort study. Diabetes Care. 2025. Link

  5. GLP-1 receptor agonists and the risk for cancer: a meta-analysis of randomized controlled trials. Diabetes, Obesity and Metabolism. 2025. Link

  6. Assessment of thyroid carcinogenic risk and safety profile of GLP1-RA semaglutide therapy for diabetes mellitus and obesity: a systematic literature review. PMC. 2024. Link

  7. Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine. 2023. Link

  8. Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Network Open. 2024. Link

  9. GLP-1 receptor agonists and cancer risk in adults with obesity. JAMA Oncology. 2025. Link

  10. Evaluating the rates of pancreatitis and pancreatic cancer among GLP-1 receptor agonists: a systematic review and meta-analysis of randomised controlled trials. Endocrinology, Diabetes & Metabolism. 2025. Link

  11. GLP-1 receptor agonists and cancer: current clinical evidence. PMC. 2025. Link

  12. Glucagon-like peptide 1 receptor agonists and cancer risk: advancing precision medicine through mechanistic understanding and clinical evidence. PMC. 2025. Link

  13. Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trial. The Lancet Regional Health - Europe. 2025. Link

  14. Use of glucagon-like peptide-1 receptor agonists does not increase the risk of cancer in patients with type 2 diabetes mellitus. Diabetes & Metabolism Journal. 2024. Link

  15. Assessing the oncological safety of glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis. Cureus. 2025. Link