GLP-1 receptor agonists tied to similar thyroid cancer risk as DPP-IV inhibitors
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Key takeaways:
- No difference in thyroid cancer risk was found for adults with type 2 diabetes using a GLP-1 receptor agonist vs. those using a DPP-IV inhibitor.
- Women may have a lower risk for thyroid cancer with GLP-1 use.
Adults with type 2 diabetes using a GLP-1 receptor agonist have a similar risk for developing thyroid cancer as those using a DPP-IV inhibitor, according to findings published in Thyroid.
Researchers collected data from adults aged 40 years and older with type 2 diabetes from Canada, Denmark, Norway, South Korea, Sweden and Taiwan who filled a prescription for a GLP-1 receptor agonist (n = 98,147) or a DPP-IV inhibitor (n = 2,488,303). Researchers found no significant difference in thyroid cancer risk between the two medication classes, with the results being consistent across all six countries and most subgroups, according to the authors.
“Our findings contribute to the growing body of evidence of the short-term safety of GLP-1 receptor agonists in relation to thyroid cancer risk,” Anton Pottegård, PhD, professor of clinical pharmacology, pharmacy and environmental medicine in the department of public health at the University of Southern Denmark, told Healio. “This provides reassurance to clinicians and patients using GLP-1 receptor agonists for the management of type 2 diabetes.”
Researchers collected cases of incident thyroid cancer diagnoses from each country’s cancer registry beginning 1 year after the first prescription fill of a GLP-1 receptor agonist or DPP-IV inhibitor medication. Follow-up continued for up to 10 years after medication began. Data were obtained from 2007 to 2023.
GLP-1s do not raise thyroid cancer risk
Incident thyroid cancer was diagnosed in 67 people using a GLP-1 receptor agonist and 6,209 adults using a DPP-IV inhibitor.
No significantly increased risk for thyroid cancer was observed for adults using a GLP-1 receptor agonist compared with those using a DPP-IV inhibitor (HR = 0.81; 95% CI, 0.59-1.12). Researchers did not identify any trend in thyroid cancer risk that was tied to increased medication doses.
No significant difference in thyroid cancer risk was observed individually in any of the six countries. In a subgroup analysis, women who used a GLP-1 receptor agonist had a lower risk for thyroid cancer than women who used a DPP-IV inhibitor (HR = 0.62; 95% CI, 0.47-0.82). When GLP-1 receptor agonist users were compared with adults who used sulfonylureas, GLP-1 receptor agonists were associated with higher risk for thyroid cancer (HR = 1.8; 95% CI, 1.28-2.52).
Pottegård told Healio that the findings are reassuring but cautioned that the median follow-up of participants in the study was short, with GLP-1 receptor agonist users followed for a median of 1.8 to 3 years and adults using a DPP-IV inhibitor followed for a median of 2.8 to 6.8 years.
“Future studies should endeavor to include populations with longer follow-up periods so risk with longer-term use can be assessed,” Pottegård said. “Further, given that thyroid cancer, in particular medullary thyroid cancer, is a rare event, future studies should leverage data from multiple large populations to ensure there is sufficient power to detect a statistically significant association if one exists.”
More research needed
In a related editorial, Juan P. Brito, MD, MSc, associate professor of medicine and consultant in the division of endocrinology at the Mayo Clinic in Rochester, Minnesota, and colleagues praised the study for its large sample size and use of multiple cohorts from different areas of the globe. They said the findings reinforce “confidence in the absence of a clinically significant short-term causal relationship between GLP-1 receptor agonists and thyroid cancer.”
The authors noted a few questions remain to be answered in future research, including why risk differs in some subgroups and why some previously published observational studies found GLP-1s may increase thyroid cancer risk.
“This discrepancy [between studies] may be explained by unmeasured confounders, such as weight and body mass index — factors associated with thyroid cancer that are notoriously challenging to capture accurately in large observational studies,” the authors wrote. “These confounders might also explain this study subgroup analysis showing a higher risk of thyroid cancer with GLP-1 receptor agonists only when compared with sulfonylureas, which might be less prescribed for obese patients due to concerns about weight gain.”
Reference:
Toro-Tobon D, et al. Thyroid. 2025;doi:10.1089/thy.2024.0690.
For more information:
Anton Pottegård, PhD, can be reached at apottegaard@health.sdu.dk.
Perspective
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GLP-1 receptor agonist labels in the U.S. (although not in Europe) have a black box warning about an increased risk for thyroid C-cell tumors seen in rats and mice. It has been difficult to establish whether GLP-1 users are truly at increased risk for the development of medullary thyroid cancer, largely because it is difficult to prove the absence of a very rare outcome. Animal models demonstrate that the C-cell effects of GLP-1 receptor agonists in rats and mice do not appear to be replicated in primates. However, randomized trials are not large enough or long enough in duration to establish whether there is a true association of GLP-1 use with thyroid cancers in humans. Recent observational studies have inconsistently reported associations of GLP-1 use with both medullary thyroid cancer and differentiated thyroid cancer, but these studies have been subject to bias.
This large multinational cohort compared thyroid cancer risks in nearly 100,000 GLP-1 and 2.5 million DPP-IV users and found no difference in risk. Study strengths include the large sample, restriction to new GLP-1 users and results that were robust in multiple sensitivity analyses. However, the number of thyroid cancer cases was small, medullary thyroid cancer risk could not be separately evaluated, and there is potential for residual confounding. Mean follow-up was 1.8 to 3 years; given that thyroid cancer likely has a long latency period, studies with longer duration are needed.
For now, given that small thyroid cancers are already being overdiagnosed, it is important to note that there is no indication to routinely screen for thyroid nodules before or during GLP-1 treatment. In addition, given the many health benefits of GLP-1 receptor agonists, their use should not be unnecessarily restricted in individuals with known thyroid nodules that have been appropriately worked up. However, for now, GLP-1s should not be used in the rare situation of patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
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