ObjectivesGlucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy has demonstrated an increased risk of thyroid C-cell hyperplasia and C-cell tumors in rodents. Due to this risk, a boxed warning for this drug class exists for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. There is a lack of data regarding any possible effect of GLP-1 RA therapy on serum thyroid levels. The objective of this case report is to describe a case of suppressed thyroid stimulating hormone levels after initiation of a subcutaneous semaglutide in a posttotal thyroidectomy patient managed with levothyroxine in order to highlight the need for closer monitoring of these patients and further research in this area. Case SummaryThe patient described in the case underwent a total thyroidectomy in 2015 with stable thyroid hormone replacement requirements with levothyroxine for 5 years until the initiation and titration of subcutaneous semaglutide. The reduction in thyroid stimulating hormone (TSH) after starting GLP-1 RA therapy necessitated a 25 percent dose reduction of levothyroxine from her original dose. Practice implicationsThis patient experienced suppressed TSH levels following initiation and titration of subcutaneous semaglutide. The etiology of these changes may be related to the direct effects of GLP-1 RA therapy on TSH levels, changes in absorption related to delayed gastric emptying rates, secondary to GLP-1 RA-associated weight loss, or a combination of these proposed mechanisms. It may be prudent to exercise more frequent monitoring of medications that require weight-based dosing and those with a narrow therapeutic index when initiating and titrating GLP-1 RA-based therapies and is an area of potential study.