Liraglutide effect on epicardial fat: Missing the forest for the trees

TO THE EDITOR: In a small clinical trial, Iacobellis and colleagues demonstrated a large reduction of epicardial adipose tissue (EAT) among subjects with type 2 diabetes treated with liraglutide as compared with subjects on metformin monotherapy (1). We are struck by the authors' overemphasis on claiming the study's observations as an independent and selective effect of liraglutide on EAT reduction while systematically minimizing the effect of massive weight loss on the adipose compartment. Although the report does not clearly articulate the magnitude of weight change that occurred during the study, we deduced this from the BMI data and calculated a −14% weight change in the liraglutide group. This degree of weight change is in striking contrast to weight reductions reported in other studies. Participants of the Liraglitude Effect and Action in Diabetes program receiving liraglutide 1.8 mg daily for 6 months had a −2.8% weight change (2). A 1-year follow-up study using a similar intervention led to a −4.8% weight change (3). Iacobellis et al. failed to address the significance of this seemingly increased efficacy of liraglutide to induce weight loss. A 36% reduction in EAT in the liraglutide group does not seem to be that unpredicted. Weight loss interventions are expected to preferentially mobilize visceral fat, including EAT, beyond what could be predicted from weight loss. In a 1-year lifestyle intervention study, subjects losing 7% of their body weight had a 26% reduction of their visceral adiposity (4). The lack of representation of anthropometric measurements such as waist circumference data is perplexing, as this information could sustain or disprove the independent effect of liraglutide on EAT thickness. Moreover, the study is credited with a power it does not possess due to the failed randomization of key characteristics such as body weight (a 17-kg weight difference between the two groups) and EAT. The differences in adiposity between the treatment and control groups could potentially influence the comparison, introducing the confounding effect of greater adiposity among the subjects receiving liraglutide. Unfortunately, there were no attempts to statistically adjust for the imbalance of this covariate. In sum, the authors position the importance of their findings by the magnitude of change in EAT. They seem to be staggered by this finding, failing to place it within the context of the massive weight loss reached by the intervention.