Putting GLP-1 RAs and Thyroid Cancer in Context: Additional Evidence and Remaining Doubts

Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study

“…Given that a potential effect of GLP1 receptor agonists on thyroid cancer is unlikely to emerge after short term use, these findings might indicate the presence of confounding. An alternative explanation for the increased risk observed in the French study, emerging early and staying at similar magnitude with increasing duration of use, could be detection bias 17. Our additional analysis indicated a nominally increased risk restricted to the first year after starting treatment, which might be consistent with an increased detection of thyroid cancer among patients using GLP1 receptor agonists.…”

Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials

“…A similar problem affects observational studies; the main survey attempting to discriminate MTC from PTC 12 used indirect markers of limited reliability. 21,22 In addition, since summaries of product characteristics issued by the main regulatory authorities include warnings about exercising caution in using GLP-1RAs in patients with a family or personal history of MTC, it is unlikely that observational studies will be able to discriminate in a reliable manner the potential effects of those drugs on the incidence of MTC in the future. Some further limitations of the present meta-analysis should be considered for a correct interpretation of its results.…”

“…The pathophysiological rationale for a potential increase in the risk of thyroid cancer determined by GLP‐1RA treatment cannot therefore be considered firmly established. In addition, epidemiological data suggesting such an association have methodological limitations, mostly related to the possibility of confounders unaccounted for in analysis 20–22 ; furthermore, other observational studies did not confirm such association 23 . Evidence from randomized clinical trials (RCTs), which are not affected by the same limitations of observational studies, may be helpful in the assessment of this important safety issue.…”

Risk of thyroid cancer associated with glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes: A population‐based cohort study

“…However, a recent commentary on this study criticized the fact that the study provided relative risk because of the inherent limitation of the case-control design and suggested that a comparison of absolute risk is necessary to evaluate fully the balance between benefit and harm. 12 Considering the previously known advantages of real-world studies compared with RCTs, 13 the limitations of real-world studies to date, and the fact that the association between GLP-1RAs and thyroid cancer is not clear in humans, our study aimed to confirm the relevant evidence to elucidate the possible thyroid cancer risk associated with incretin-based therapies. In this study, we investigated whether GLP-1RAs or DPP-4 inhibitors had different effects on the risk of thyroid cancer compared with sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are not known to be associated with an increased risk of thyroid cancer.…”

“…This was a well‐designed nested case‐control study analysing a real‐world nationwide health care database, and the results remained consistent in stratified and sensitivity analyses. However, a recent commentary on this study criticized the fact that the study provided relative risk because of the inherent limitation of the case‐control design and suggested that a comparison of absolute risk is necessary to evaluate fully the balance between benefit and harm 12 …”