TY - JOUR
T1 - Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer
T2 - An International Multisite Cohort Study
AU - Baxter, Sarah M.
AU - Lund, Lars Christian
AU - Andersen, Jacob H.
AU - Brix, Thomas H.
AU - Hegedüs, Laszlo
AU - Hsieh, Miyuki Hsing Chun
AU - Su, Chris Tzu Ting
AU - Cheng, Michael Chun Yuan
AU - Chang, Zoe Chi Jui
AU - Lai, Edward Chia Cheng
AU - Hussain, Swaleh
AU - Chu, Cherry
AU - Gomes, Tara
AU - Antoniou, Tony
AU - Eskander, Antoine
AU - Bouck, Zachary
AU - Tadrous, Mina
AU - Bea, Sungho
AU - Choi, Eun Young
AU - Shin, Ju Young
AU - Modig, Karin
AU - Talbäck, Mats
AU - Ljung, Rickard
AU - Gulseth, Hanne Løvdal
AU - Karlstad, Øystein
AU - Hicks, Blánaid
AU - Pottegård, Anton
PY - 2025/1
Y1 - 2025/1
N2 - Introduction: Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. Methods: This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model. Results: We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. Discussion: In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short follow-up.
AB - Introduction: Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. Methods: This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model. Results: We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. Discussion: In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short follow-up.
KW - active comparator
KW - dipeptidyl peptidase-4 inhibitors
KW - glucagon-like peptide 1 receptor agonists
KW - thyroid cancer
U2 - 10.1089/thy.2024.0387
DO - 10.1089/thy.2024.0387
M3 - Journal article
C2 - 39772758
AN - SCOPUS:85214587146
SN - 1050-7256
VL - 35
SP - 69
EP - 78
JO - Thyroid
JF - Thyroid
IS - 1
ER -