Indeed, monogenetic approaches often fall short of treating polygenetic diseases such as diabetes, and thus patients often require different drugs for effective disease control. (4) They argued that the therapeutic success of GLP-1 agonists in diabetes, whose glucose-lowering action relies on GLP-1 receptors in different tissues, shall be an inspiration to develop treatments that act on different molecular targets. provided a Perspective on polypharmacology in diabetes. (3) The article explains how the glucose-lowering activity of GLP-1 was elucidated, and how the rapid elimination of GLP-1 led to the development of liraglutide, a fatty-acid-conjugated derivative of GLP-1 whose glucose-lowering action spans 24 h. Lotte Knudsen contributed a Drug Discovery Stories feature on the history of the glucagon-like peptide-1 (GLP-1) analogue liraglutide. This Virtual Issue features articles on the pharmacology and safety of approved diabetes treatments. (2) Global diabetes-related health care costs were estimated at 966 billion USD in 2021, and are projected to reach 1,054 billion USD by 2045. According to the International Diabetes Foundation, an estimated 537 million people were living with diabetes in 2021, and the number of patients is projected to reach 783 million by 2045. (1) The high and rapidly growing prevalence of diabetes presents significant challenges to the health care system. (1) Chronic diabetes-related complications affect several organs and include retinopathy, nephropathy, peripheral neuropathy, peripheral arterial disease, and diabetic foot ulcers. (1) Insulin deficiency and hyperglycemia result from the destruction of pancreatic beta cells by an autoimmune reaction in type 1 diabetes, or from a reduced response to insulin (insulin resistance) and decreased insulin production by beta cells in type 2 diabetes. Diabetes mellitus is defined as “a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both”.