12602 The Effect of Three-Month Semaglutide Treatment on Serum TSH and Thyroid Hormones in Individuals with Obesity

Abstract Disclosure: P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. A.J. Kretowski: None. L. Szczerbinski: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a crucial role in managing obesity and diabetes, significantly influencing glycemic control and weight management. Previous studies showed that GLP-1 RAs therapy affects thyroid-stimulating hormone (TSH) levels; however, they were limited by small sample sizes and did not extensively cover newer agents like semaglutide. Thus, the aim of this study was to assess the impact of a three-month semaglutide treatment on thyroid hormones and TSH levels in individuals with obesity, without diabetes, and examine the relationship of these changes with weight loss. Methods: We analyzed data from 290 patients participating in the GAROS study, excluding those on medications affecting thyroid function or with a known history of thyroid disease. All participants underwent a three-month treatment with oral semaglutide, followed by a three-month discontinuation phase. Measurements of TSH, free triiodothyronine (fT3), free thyroxine (fT4), and body weight were taken at baseline, at the end of the treatment period, and three months post-treatment discontinuation. To compare changes in TSH, fT3, and fT4 levels, as well as weight, across the study timelines we used non-parametric tests due to the non-normal distribution of the data. We also employed multiple linear regression models to evaluate the association between thyroid hormone changes and weight loss, both in the aggregate and stratified by sex. Results: Initial fT3, fT4, and TSH levels were 3.13 pg/ml (SD=0.38), 0.94 ng/dl (SD=0.10), and 1.64 mIU/l (SD=0.82), respectively. Post-treatment, fT3 decreased on average by 0.33 pg/ml (p<0.001), TSH by 0.32 mIU/l (p<0.001), and fT4 increased by 0.06 ng/dl (p<0.001). Upon discontinuation, fT3 and fT4 levels did not fully return to baseline values but showed a significant shift in that direction (p<0.001 for fT3 and p=0.006 for fT4, compared to baseline). Conversely, TSH levels adjusted back to their baseline values (p=0.26). Notably, changes in fT4 levels, unlike fT3 and TSH, were significantly negatively associated with weight changes during (p=0.030) and post-treatment (p=0.008), across sex-stratified analyses. Conclusions: Semaglutide treatment significantly alters thyroid hormones and TSH levels in patients with obesity, with some effects reversible post-discontinuation. Except for fT4, these hormonal changes appear to be independent of the weight loss effects of semaglutide. Although the magnitude of these alterations might not be clinically significant, they do imply that GLP-1 RAs may have additional physiological effects. The exact nature of the interaction between semaglutide and thyroid function, however, remains to be fully elucidated, highlighting the need for further research to clarify these mechanisms. Presentation: 6/2/2024