BACKGROUND: Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and associated with a more severe phenotype and worse outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists have recently been shown to improve cardiovascular outcomes in patients with obesity. However, their impact on patients with obesity and HCM is unclear. Therefore we sought to assess the safety and efficacy of GLP-1 agonists in patients with obesity and HCM. METHODS: Using the TriNetX Global Research Network, patients with HCM and BMI ≥30 kg/m RESULTS: Of 29,521 patients with HCM, 1553 (5 %) received GLP-1 agonists. After propensity score matching, both groups (n = 1497 in each) had comparable baseline characteristics. Over a 2-year follow-up period, patients with HCM on GLP-1 agonists had a significant reduction in BMI and lower all-cause mortality and HF hospitalization rates compared to patients not on GLP-1 agonists. In contrast, there was no significant differences in new-onset atrial fibrillation or ventricular arrhythmia, nor was there a significant difference in safety events related to GLP-agonist use. CONCLUSION: In this large real-world dataset, the use of GLP-1 agonists in patients with obesity and HCM was associated with improved survival and lower rates of HF hospitalization. These data support future large prospective clinical trials of GLP-1 agonists in patients with obesity and HCM.