Kim et al. used in vitro and mouse studies to identify a gut–heart axis involved in the regulation of blood pressure. In this axis, activation of the glucagon-like peptide-1 receptor (GLP-1R) leads to secretion of atrial natriuretic peptide (ANP) and reduction in blood pressure. Furthermore, the Rap guanine nucleotide exchange factor Epac2 (also known as Rapgef4) was identified as a downstream target of GLP-1R in cardiomyocytes. The investigators call for more research on the metabolic and cardiovascular effects of ANP as a downstream target of GLP-1 action.