SUN-637 - Impact of GLP-1 Agonist Therapy on TSH Levels in Hypothyroid Patients

Introduction:
GLP-1 agonists have been a growing medication class, widely used for the management of DM and obesity. Their metabolic effects are primarily exerted through glucose-dependent insulin secretion, suppression of glucagon release and delayed gastric emptying. There has been growing evidence about their effect on other endocrine axes, including the hypothalamic-pituitary-thyroid axis, with preclinical evidence suggesting the expression of GLP-receptors in TRH-releasing nuclei in the hypothalamus. In view of such potential influence, we aim to investigate the effect of initiating GLP-1 agonists in patients with hypothyroidism who are receiving a stable dose of Levothyroxine on TSH levels.

Methods: We conducted a retrospective cohort study using TriNetX, a federated global research network aggregating de-identified electronic medical records from large healthcare organizations. Adult patients with diabetes mellitus, Hypothyroidism on Levothyroxine therapy and with normal TSH range (0.5-4.5 mIU/L) were included, patients who are pregnant or have a history of thyroid cancer were excluded. Patients were stratified into two groups: those who received GLP-1 agonists and those who did not. Propensity score matching (1:1) was performed to balance cohorts by age, sex, obesity, CKD, CHF, Liver disease, chronic use of Omeprazole and Nicotine dependence. The primary outcome was the change in the level of TSH after starting treatment at 1-month, 6-month and 12-month intervals. A Two-sample T-test analysis was used to compare the two groups with p-values calculated to assess statistical significance.

Results: A total of 137,217 patients were included in each cohort. The mean age and percentage of females were comparable between the two groups: 61.2 years and 73.7% in the GLP-1-treated cohort, and 61.0 years and 73.5% in the non-GLP-1 cohort. Regarding TSH levels, the GLP-1-treated cohort exhibited a mean TSH of 3.220 ± 6.265 mIU/L at 1 month, 2.653 ± 9.244 mIU/L at 6 months and 2.559 ± 9.816 mIU/L at 12 months. In contrast, the non-GLP-1 cohort had a mean TSH of 4.266 ± 16.145 mIU/L at 1 month, 3.093 ± 12.448 mIU/L at 6 months and 2.966 ± 13.677 mIU/L at 12 months. Two-sample t-tests demonstrated statistically significant differences between the GLP-1-treated and non-GLP-1 cohorts at all time intervals with p< 0.001: 1 month (t = -6.039, df = 4864), 6 months (t = -6.506, df = 103488) and 12 months (t = -6.796, df = 155220).

Conclusion: Our study provides compelling evidence that the initiation of GLP-1 agonists in patients with hypothyroidism is associated with a significant reduction in TSH levels over time. The observed decline suggests that GLP-1 agonists may influence thyroid function, which highlights the importance of monitoring thyroid function in patients initiating GLP-1 agonist therapy, particularly those with hypothyroidism, to ensure optimal thyroid hormone replacement therapy.

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