JAAD CME Part 1: Mechanism of Action of GLP-1 Receptor Agonists and Potential Pathways in Skin Health.

Abstract

The prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise in the United States (U.S.) and worldwide, contributing to substantial morbidity and mortality through metabolic dysfunction and systemic inflammation. Glucagon-like peptide-1(GLP-1)-based therapies, originally developed for glycemic control, have since demonstrated significant weight loss benefits and multiple effects across multiple organ systems. This review provides an overview of the historical development and mechanistic underpinnings of GLP-1 receptor agonists (GLP-1RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, with emphasis on their broad cellular distribution and physiologic actions. Beyond their well-established roles in glucose regulation and β-cell function, GLP-1-based agents exert immunomodulatory effects, attenuating pro-inflammatory cytokine signaling while promoting anti-inflammatory pathways. Emerging evidence may support their relevance in dermatology, including improvement in psoriasis and hidradenitis suppurativa (HS), enhanced wound healing, and modulation of nociceptive signaling. These findings underscore the expanding therapeutic scope of GLP-1-based agents, suggesting potential utility in both systemic metabolic disease and dermatologic conditions. Continued investigation is warranted to clarify receptor-specific mechanisms in skin biology and to optimize integration of these therapies into dermatologic practice.