SUN-350 - Cardiovascular Outcomes in Patients with Hypothyroidism Treated with GLP-1 Receptor Agonists: A Real-World Propensity-Matched Analysis from the Trinetx Network.

Hypothyroidism is associated with dyslipidemia, endothelial dysfunction, and elevated cardiovascular risk. Levothyroxine still remains the cornerstone of treatment; however, it does not mitigate the cardio-metabolic risks. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardioprotective benefits in diabetes and obesity, yet their effects in hypothyroid populations remain unclear. This study evaluated cardiovascular outcomes among hypothyroid patients receiving GLP-1RAs versus those not treated with these agents.
Using the global TriNetX Research Network (107 healthcare organizations), adults (≥18 yr) with hypothyroidism on levothyroxine were identified. Cohort A received GLP-1RAs; Cohort B did not. After 1:1 propensity matching for demographics, comorbidities, and medications, each cohort included 141,286 patients. Outcomes over 5 years included major adverse cardiovascular events (MACE-1: myocardial infarction, stroke, or death; MACE-2: MACE-1 + revascularization), hospitalization, mortality, acute coronary syndrome (ACS), cerebrovascular accident (CVA), revascularization, and LDL levels.
Baseline characteristics were balanced (mean age 58 yr; 79% female). GLP-1RA use was associated with lower risk of: MACE-1 9.4% vs 17.4% (RR 0.54, 95% CI 0.53–0.55), MACE-2 9.9% vs 18.1% (RR 0.55, 0.54–0.56), mortality 3.7% vs 9.9% (RR 0.37, 0.36–0.38), hospitalization 40.4% vs 54.7% (RR 0.74, 0.73–0.75), ACS 3.6% vs 5.4% (RR 0.67, 0.65–0.70), CVA 3.7% vs 5.5% (RR 0.67, 0.65–0.69), and revascularization 1.3% vs 1.9% (RR 0.70, 0.66–0.74); all p < 0.001. Mean LDL was slightly lower with GLP-1RAs (90.3 ± 37.6 vs 92.9 ± 38.2 mg/dL, p < 0.001).
In this real-world analysis of patients with hypothyroidism on levothyroxine, GLP-1RA therapy was associated with markedly reduced risks of major cardiovascular events, hospitalization, and all-cause mortality over 5 years.
These findings extend GLP-1RA cardiovascular benefits to hypothyroid populations. Furthermore, the results highlight the need for mechanistic studies to elucidate how GLP-1RAs interact with thyroid hormone pathways and vascular physiology. As an observational analysis, these associations may be influenced by residual confounding despite propensity matching, including more frequent healthcare utilization among GLP-1 RAs users, and should be interpreted as hypothesis generating. Ultimately, this research supports a paradigm shift toward integrated cardiometabolic care in hypothyroidism, leveraging GLP-1RAs as a potential adjunct to traditional hormone replacement therapy.

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