Background Increased cardiac adipose tissue is associated with cardiovascular morbidity in type 2 diabetes. We hypothesized that treatment with liraglutide can reduce cardiac adipose tissue. Materials and methods LIRAFLAME is a randomized placebo-controlled, double-blind, parallel clinical study. Participants with type 2 diabetes were randomized to treatment with liraglutide 1.8 mg/day or placebo for 26 weeks. Computed tomography was performed at baseline and end-of-treatment to evaluate the cardiac adipose tissue volume, quantified automatically. We report the results of a secondary endpoint evaluating changes in cardiac adipose tissue. Results A total of 102 participants were randomly assigned to liraglutide (n = 51) or placebo (n = 51). At baseline, the mean (SD) cardiac adipose tissue volume was comparable between the liraglutide and the placebo group [232.6 (112.8) vs 227.0 (103.2) ml, p = 0.80]. Mean change in body weight was −3.7 (−4.8, −2.6) kg in the liraglutide and − 0.18 (−0.76, 0.40) kg in the placebo group. From baseline to end-of-treatment the mean cardiac adipose tissue change was −11.5 (95 −17.6, −5.4) ml in the liraglutide (p textless 0.001) and − 0.01 (−5.3, 5.3) ml in the placebo (p = 1.00) groups. The reduction in cardiac adipose tissue was significantly larger in the liraglutide compared to the placebo group (mean difference: −11.4 [−19.4, −3.3] ml, p = 0.006), but significance was lost after adjustment for changes in body mass index (P = 0.46). Conclusion Treatment with liraglutide for 26 weeks was associated with a reduction in cardiac adipose tissue compared to placebo. The reduction was not independent of weight-loss, suggesting that this is not a drug-specific effect.