Effects of semaglutide versus dulaglutide on epicardial fat thickness in subjects with Type 2 diabetes and obesity

Abstract

Background and Aims. Epicardial adipose tissue (EAT), the visceral fat depot of the heart, is a modifiable cardio-metbolic risk factor and therapeutic target. Semaglutide and dulaglutide, glucagon-like peptide-1 (GLP-1) receptor agonists, are indicated for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists have recently shown to reduce cardiovascular risk. Epicardial adipose tissue expresses GLP-1 receptors (GLP-1Rs). GLP-1 receptor agonist liraglutide is known to significantly decrease EAT thickness. However, the effects of GLP-1 receptor agonists semaglutide and dulaglutide on EAT thickness are unknown. Materials and Methods. We performed a 12-week, controlled, parallel study in 80 subjects with T2DM and obesity. Patients received either semaglutide, up to 1 mg subcutaneous (sc) weekly, or dulaglutide, up to 1.5 mg sc weekly, as the standard of care in addition to their usual medication regimen. Twenty subjects with T2DM and obesity were started on metformin and a diet and served as the control group. Ultrasound-measured EAT thickness was measured at baseline and at the 12-week follow-up. Results. Epicardial adipose tissue thickness significantly decreased in both semaglutide and dulaglutide groups (P < 0.001) after 12 weeks, accounting for a 20% reduction. There was no EAT reduction in the metformin group. Body mass index (BMI) and HbA1c improved in all groups without reaching statistical significance. Epicardial adipose tissue thickness reduction was significantly greater (P < 0.01) with the higher doses of semaglutide (1 mg) and dulaglutide (1.5 mg), respectively. Conclusion. Weekly administration of either GLP-1 receptor agonists semaglutide or dulaglutide causes a rapid, substantial, and dose-dependent reduction in EAT thickness.