Drug Discovery and Development of Semaglutide and Tirzepatide from the Gila monsters (Heloderma spp)

The archetypical venomous lizard species are the helodermatids, the Gila monsters (Heloderma suspectum), and the beaded lizards (Heloderma horridum). Biological significance: The helodermatid lizards are the classical venomous lizards, and the pharmacological potential of the venom from these species has been known for years; best illustrated by the identification of exendin-4, which is now used in the treatment of type 2 diabetes. Heloderma venoms contain a complex mixture of biologically active proteins and enzymes, many of which are similar to those found in snakes. Exendin-4, a glucagon-like peptide-1 (GLP1) receptor agonist, was derived from Heloderma venom and has been developed into the diabetes drug exenatide. The potent effect of exendin-4 in stimulating insulin secretion has shown that it mimics glucagon-like peptide-1 (GLP-1), in most if not all of its actions. Thus, like GLP-1, exendin-4 inhibits glucagon secretion and stimulates insulin synthesis. Research into extendin-4 yielded semaglutide and tirzepatide. Both semaglutide and tirzepatide are well-known as (GLP-1) receptor agonists widely studied and used to manage type 2 diabetes. The journey of drug discovery to develop anti-obesity drugs began with identifying the role of GLP-1 receptor agonists in appetite control. Tirzepatide can lead to more pronounced weight loss compared to semaglutide, but the real mechanisms underlying their extraordinary effectiveness in weight loss lie in their effects on the brain. The gastrointestinal tract contains specialized cells that measure the quantities and qualities of incoming food (as well as the absence of food) and communicate this with the rest of the body, including the brain. The brain starts the process of releasing digestive juices and even causes insulin levels to rise.