SAT-306 - Thyroid Trade-Offs: GLP-1 Receptor Agonists and Levothyroxine in Hypothyroidism: A Global Propensity Score-Matched Analysis

GLP-1 receptor agonists (GLP-1RAs) induce significant weight loss and delay gastric emptying, factors that may affect levothyroxine absorption and thyroid hormone requirements. Emerging data suggest GLP-1RA–associated weight reduction may lower thyroid-stimulating hormone (TSH) levels in patients treated for hypothyroidism, raising concern for potential thyroid hormone over-replacement if monitoring is inadequate. This study aimed to quantify changes in TSH and assess associated clinical outcomes in a large real-world cohort.
We conducted a retrospective propensity score–matched (PSM) cohort study using the TriNetX Analytics Network (2010–2022), including patients with hypothyroidism receiving GLP-1RAs (n=124,968) and matched controls not receiving GLP-1RAs (n=1,149,022). One-to-one PSM was performed using greedy nearest-neighbor matching with a caliper of 0.1 pooled standard deviations, adjusting for 42 baseline characteristics including demographics, comorbidities, laboratory values, and cardiovascular medications. Primary outcomes were all-cause mortality, heart failure (HF), and TSH levels. Secondary outcomes included all-cause hospitalization, ICU admission, acute kidney injury (AKI), ischemic stroke/TIA, and depression. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated over 5 years, and t-tests compared laboratory values.
After matching, 82,520 pairs were analyzed (mean age 60.1±12.9 years; ~78% female). GLP-1RA use was associated with significantly lower odds of all-cause mortality (OR 0.254; 95% CI 0.246–0.264; P< 0.001) and HF (OR 0.579; 95% CI 0.565–0.594; P< 0.001). Mean TSH levels were significantly lower in GLP-1RA users compared with controls (mean difference −2.06 mIU/L; 95% CI −2.35 to −1.78; P< 0.001). GLP-1RA therapy was also associated with reduced odds of hospitalization (OR 0.475), ICU admission (OR 0.464), AKI (OR 0.679), ischemic stroke/TIA (OR 0.618), and depression (OR 0.907) (all P< 0.001).
In this large propensity score–matched real-world cohort, GLP-1 receptor agonist use in levothyroxine-treated patients with hypothyroidism was associated with a clinically meaningful reduction in TSH levels. These findings suggest that initiation of GLP-1RA therapy may alter thyroid hormone requirements, potentially related to weight loss or metabolic effects. This association underscores the importance of routine thyroid function monitoring and timely levothyroxine dose adjustment following GLP-1RA initiation. Prospective studies are needed to clarify underlying mechanisms and inform optimal monitoring strategies in clinical practice.

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