Objective: Epicardial adipose tissue (EAT), the visceral fat depot of the heart, is a modifiable cardiovascular risk factor and emerging therapeutic target. Liraglutide, an analog of glucagon-like peptide-1, is indicated for the treatment of type 2 diabetes mellitus. Liraglutide has recently been shown to reduce cardiovascular risk. Nevertheless, whether liraglutide could reduce EAT is unknown. Methods: To test the hypothesis, a 6-month randomized, open-label, controlled study was performed in 95 type 2 diabetic subjects with body mass index (BMI) ≥27 kg/m2 and hemoglobinA1c ≤8% on metformin monotherapy. Individuals were randomized in two groups to receive additional liraglutide up to 1.8 mg s.c. once daily (n = 54) or to remain on metformin up to 1,000 mg twice daily (n = 41). Ultrasound-measured EAT thickness was measured at baseline and at 3- and 6-month follow-ups. Results: In the liraglutide group, EAT decreased from 9.6 ± 2 to 6.8 ± 1.5 and 6.2 ± 1.5 mm (P < 0.001), accounting for a −29% and −36% of reduction at 3 and 6 months, respectively, whereas there was no EAT reduction in the metformin group; BMI and hemoglobinA1c improved only in the liraglutide group after 6 months. Conclusions: Liraglutide causes a substantial and rapid EAT reduction. Liraglutide cardiometabolic effects may be EAT-mediated.