HX05 From toxic bite to therapeutic benefit: the Gila monster and the history of glucagon-like peptide-1 agonists

Abstract

Obesity is associated with multiple dermatological conditions, including inflammatory dermatoses, poor wound healing, cutaneous infections, lymphoedema and possibly skin cancer. Glucagon-like peptide (GLP)-1 receptor agonists, including semaglutide and liraglutide, have transformed management of obesity and diabetes. They are of emerging relevance to dermatology, producing weight loss effects with potential anti-­inflammatory and immunomodulatory benefits. This review examines the history of GLP-1 agonists, from bioactive peptides in Gila monster venom to the development of modern therapeutics. We outline the discovery of GLP-1 agonists and their emerging relevance to dermatology. A structured review of PubMed and historical sources (from 1898 to January 2026) was undertaken. The Gila monster is one of only two venomous lizards worldwide and is native to the southwestern USA and northwestern Mexico, with early observations in the Gila River basin. In 1869, Professor Cope described the species and named it ‘Heloderma suspectum’, reflecting its studded skin and presumed toxicity. Among the Navajo, it is revered for spiritual powers and its trembling forefoot is believed to identify traditional healers. Envenomation is well described; fatalities are rare, although a pet bite was fatal in February 2024. Interest arose from its extreme metabolic efficiency, with it consuming only three to four meals annually. In 1982, venom-stimulated pancreatic secretion was demonstrated in guinea pigs. In 1992, endocrinologist Dr John Eng isolated exendin-4 from salivary glands. Extendin-4 is structurally similar to human GLP-1 but more resistant to degradation. Despite initial pharmaceutical disinterest, Eng partnered with Amylin to develop exenatide (Byetta), which became the first FDA-approved GLP-1 agonist for type 2 diabetes mellitus in 2005. Longer-acting agents followed, including semaglutide (2021). Emerging evidence supports GLP-1 agonists in dermatology, including adjunctive treatment for obesity-associated hidradenitis suppurativa. The Gila monster, first named for its suspected toxicity, underpinned therapeutics that have transformed obesity management and are increasingly relevant to dermatology.