Implications of Glucagon-like Peptide-1 Receptor Agonists on Thyroid Function and Thyroid Nodules: A Drug Target Mendelian Randomization and Cohort Study.

OBJECTIVES

Glucagon-like Peptide-1 receptor agonists (GLP-1RAs) are antidiabetic medications, with conflicting reports about their relationship with thyroid diseases. This study investigates their effects on thyroid function and nodules in patients with diabetes.

METHODS

Mendelian randomization was conducted to examine the association between genetically proxied GLP-1RA activity and thyroid diseases. This was followed by a cohort study involving 169 patients with diabetes, who were divided into a control group (control group, W/O GLP-1 treatment) and a GLP-1RA treatment group (GLP-1RAs group) based on their medication usage. Patients' thyroid function tests, thyroid nodule diameters, and Thyroid Imaging Reporting and Data System classifications were compared at baseline and after 12 months of treatment.

RESULTS

Through Mendelian randomization, GLP-1RAs decrease free thyroxine (fT4) levels within the normal range [odds ratio (95% CI) = 0.9948 (0.9936-0.9961), P < .001]. Cohort study showed that after treatment, the nodule diameter increased in both the control group (0.69 vs 0.77, P = .004) and the GLP-1 group (0.68 vs 0.71, P = .019). In the GLP-1 group, the Thyroid Imaging Reporting and Data System (2.60 vs 2.69, P = .007) levels increased, while the fT4 (1.26 vs 1.17, P = .005) levels decreased. However, linear regression did not show significant association between GLP-1 and post-treatment differences in thyroid function or thyroid nodule.

CONCLUSIONS

GLP-1RAs treatment of 12 months in patients with diabetes is considered relatively safe regarding thyroid disease although there is a potential risk for decreasing of fT4 levels and nodule growth/progression, with no clear evidence of superiority over other antidiabetic treatments.