GLP-1 Receptor Agonists Show Promise in Chronic Inflammatory Skin Diseases by Modulating Immunometabolic Pathways

Chronic immune-mediated inflammatory diseases (IMIDs), including psoriasis, hidradenitis suppurativa (HS), and atopic dermatitis (AD), are increasingly recognized as systemic immunometabolic disorders. These conditions involve chronic immune activation and elevated proinflammatory mediators, often co-occurring with obesity, insulin resistance (IR), and metabolic syndrome. Current treatments often fall short in addressing both the immune dysregulation and metabolic comorbidities. Glucagon-like peptide-1 (GLP-1), an incretin hormone known for glucose homeostasis and weight regulation, also exhibits broad tissue expression of its receptor, GLP-1R, suggesting roles beyond metabolism, particularly in inflammation.

This comprehensive review synthesized current literature on GLP-1 receptor agonists (GLP-1RAs) in chronic inflammatory skin diseases (CISDs), exploring their immunometabolic mechanisms and translational perspectives. Researchers analyzed preclinical and clinical data to elucidate how GLP-1R signaling impacts both skin cells, such as keratinocytes, and various immune cells present within inflammatory lesions. The review specifically focused on conditions like psoriasis, hidradenitis suppurativa (HS), and atopic dermatitis (AD), examining the interplay between immune dysregulation and metabolic disturbances in these contexts. The authors aimed to identify the potential therapeutic utility of GLP-1RAs by mapping their known metabolic and emerging anti-inflammatory effects to the pathophysiology of CISDs.

The review highlights that GLP-1R is expressed on various immune cells and skin cells, including keratinocytes, within inflammatory lesions, suggesting a direct role for GLP-1R signaling in modulating cutaneous inflammation. GLP-1RAs exert their beneficial effects through multiple immunometabolic pathways, including improved glucose homeostasis, reduced insulin resistance, and significant weight reduction, all of which indirectly ameliorate inflammatory burdens. Directly, GLP-1RAs demonstrate anti-inflammatory and immunomodulatory properties by influencing immune cell function and cytokine profiles. > Evidence for the therapeutic potential of GLP-1RAs is particularly pronounced in psoriasis and hidradenitis suppurativa (HS), where strong links to metabolic dysfunction exist, indicating that these agents can mitigate both the dermatological symptoms and associated metabolic comorbidities. While the connection is less clear for atopic dermatitis (AD), emerging data suggest a growing body of evidence linking AD to metabolic disorders, implying future potential. These agents can reduce systemic inflammation by modulating pathways like NF-κB and MAPK, thereby decreasing the production of proinflammatory cytokines.