A Closer Look at the Dermatological Profile of GLP-1 Agonists

Abstract

Background/objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in treating type 2 diabetes and obesity, offering established metabolic and cardiovascular benefits. Emerging evidence suggests these agents also exert direct dermatologic effects. This systematic review categorizes these effects and explores their role in inflammatory skin diseases.

Methods: A comprehensive literature search was performed across EMBASE, PubMed, Web of Science, and Google Scholar for studies published from 2014 to 2025. Inclusion criteria were English-language, peer-reviewed original research involving human subjects that linked GLP-1RAs to dermatologic effects. Animal and in vitro studies were excluded. PRISMA guidelines were followed.

Results: Fifty-one studies met inclusion criteria. Thirty-four reported adverse effects, including hypersensitivity, injection-site reactions, pruritus, urticaria, angioedema, and immune-mediated conditions like bullous pemphigoid. Seventeen studies described beneficial outcomes, such as improvements in psoriasis, reduced hidradenitis suppurativa flares, enhanced wound healing, anti-aging potential, and decreased inflammation. GLP-1RAs showed cytokine modulation in psoriasis, though their role in hidradenitis suppurativa remains uncertain. Cosmetic concerns, such as "Ozempic Face" due to rapid weight loss, were also noted.

Conclusions: GLP-1RAs have a broad spectrum of dermatologic effects, from immunomodulatory benefits to adverse cutaneous reactions. Their impact on inflammatory skin disorders suggests a novel therapeutic avenue. However, adverse reactions and aesthetic changes warrant vigilance. Future research should focus on mechanistic studies, long-term safety, and identifying biomarkers to predict dermatologic responses, ultimately guiding personalized treatment approaches.

Keywords: GLP-1 receptor agonists; dermatological side effects; hidradenitis suppurativa; hypersensitivity reactions; immune modulation; inflammatory skin diseases; injection site reactions; metabolic changes; psoriasis; weight loss.

Figure 1

The figure illustrates the mechanism of GLP-1RAs. It shows GLP-1 binding to its receptor on pancreatic beta cells, activating intracellular signaling via adenylate cyclase and increasing cAMP. This triggers pathways involving PKA and Epac2, leading to enhanced insulin secretion, reduced glucagon release, delayed gastric emptying, and appetite suppression. The effects are depicted with arrows and labels across pancreatic, gastrointestinal, and central nervous system targets.

Figure 2

The figure illustrates the physiological actions of GLP-1 in a clear, flat-design style. It shows that GLP-1 stimulates insulin secretion from the pancreas, delays gastric emptying, and promotes satiety by acting on the brain. It also helps lower blood glucose by reducing hepatic glucose output. Together, these actions support appetite control and improved glycemic regulation.

Figure 3

PRISMA flowchart.

Figure 4

Immunomodulatory effects of GLP-1RAs. This figure illustrates the immunomodulatory effects of GLP-1 receptor agonists, independent of weight loss. It shows that GLP-1RAs reduce pro-inflammatory markers such as TNF-α, IL-17, IL-6, and C-reactive protein, while also blocking the NF-κB signaling pathway. A histological skin section highlights decreased epidermal thickness, linking these molecular effects to observed clinical improvements in conditions like psoriasis.

Figure 5

Potential GLP-1RA influence on Hsp70 in skin cells. The figure shows a cross-section of skin highlighting keratinocytes and the proposed effect of GLP-1 receptor agonists on Hsp70 expression. GLP-1RAs bind to the GLP-1 receptor, activating the ERK signaling pathway, which may lead to increased Hsp70 production. Hsp70, shown both inside and outside cells, functions in cellular protection and immune signaling. While direct skin evidence is lacking, the diagram illustrates a speculative pathway linking GLP-1RA, ERK activation, and heat shock protein-mediated immune modulation.