Background: Cumulative evidence strongly implicates that the disruption of clock genes (CGs) plays a causative role in insulin resistance, hyperglycemia and β-cell dysfunction in type 2 diabetes (T2D). CGs are synchronized by meal timing. Indeed, in animals and patients with T2D, restricting feeding to specific hours, such as large meals assigned to breakfast with reduced dinner, can reset and restore CG expression, resulting in improved glycemic control, insulin sensitivity and reduction of HbA1c compared to isocaloric diet with a different meal timing (small breakfast and overeating at dinner). Since glucagon-like peptide-1 (GLP-1) is secreted within a few minutes in response to food ingestion and it influences multiple humoral and neural signaling pathways that may further influence CG expression in many cells, it has been suggested that GLP-1 may be a resetting signal for the CGs, synchronizing the food entrainment on CGs expression thereby influencing the glucose metabolism. In fact, several studies in animal models, documented that GLP-1 analogs either exenatide or liraglutide, via activation of CG expression and AMPK-SIRT-1 pathway, improved insulin sensitivity, muscular glucose uptake, reduced hepatic and cardiac steatosis, inflammatory cytokines and oxidative stress, and enhanced β-cell insulin secretion and proliferation, independently of the GLP-1 analog glucose-lowering effects.