Gopinath, Shilpa

BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have expanded from metabolic therapeutics to agents with broad effects on inflammation, tissue repair, cutaneous and adipose biology, and aging-related pathways. Clinicians increasingly encounter cutaneous manifestations and aesthetic sequelae with important implications for dermatologic counseling and multidisciplinary care. OBJECTIVE To review current evidence regarding GLP-1RA effects on skin biology, inflammatory dermatoses, wound healing, cutaneous adverse events, and aesthetic aging. MATERIALS AND METHODS A narrative review of clinical, translational, and mechanistic literature was performed, emphasizing psoriasis, hidradenitis suppurativa, wound repair, skin hypersensitivity reactions, autoimmune blistering disease, and facial volume loss associated with pharmacologic weight reduction. RESULTS GLP-1RAs are hypothesized to improve inflammatory skin conditions and wound repair through anti-inflammatory, immunometabolic, and proreparative pathways. Yet, their use may also be associated with injection-site reactions, hypersensitivity eruptions, rare autoimmune blistering disorders, and clinically significant facial deflation and skin laxity. Current evidence is strongest for mechanistic plausibility and observational clinical signals, whereas dermatology-specific randomized trials remain limited. CONCLUSION GLP-1RAs exert bidirectional effects on cutaneous biology. Recognition of both therapeutic opportunities and potential aesthetic or adverse sequelae is important, with patient counseling ideally occurring within a multidisciplinary framework that integrates metabolic benefits with skin health and appearance.

BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert systemic metabolic and anti-inflammatory effects that may be relevant to cellular senescence, a key driver of skin aging. However, human cutaneous data are lacking. OBJECTIVE To explore whether systemic GLP-1RA therapy translates to a detectable reduction in cutaneous senescence, quantified by epidermal p21 expression and supported by AI-driven facial imaging. MATERIALS AND METHODS In this controlled observational pilot study, 3 male adults (GLP-1RA n = 2; GLP-1RA–naïve control n = 1) underwent 3-mm punch biopsies from a standardized, sun-protected gluteal site to isolate intrinsic aging. Senescence was quantified through blinded whole-epidermis digital annotation of p21-positive nuclei. Clinical phenotypes were assessed using noninvasive cheek measurements and AI-based facial age estimation. RESULTS The cohort demonstrated divergence in senescence-associated biomarkers correlating with GLP-1RA exposure. The GLP-1RA–naïve control exhibited 8.0% ( n = 2,062 nuclei) epidermal senescence. By contrast, participants with 163 and 62 days of GLP-1RA exposure showed reduced senescence burdens of 2.4% ( n = 2,045) and 0.6% ( n = 1,636), respectively. Automated facial age estimation remained concordant with chronological age across subjects. CONCLUSION Systemic GLP-1RA exposure is associated with a substantial reduction in epidermal p21 expression in some subjects, suggesting a senomorphic effect and supporting further mechanistic studies at the interface of metabolic regulation and skin aging.