Glucagon-like peptide-1 receptor agonists in psoriasis and psoriatic arthritis: emerging evidence and future research opportunities.

BACKGROUND: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated diseases often associated with obesity, metabolic syndrome, and type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, exert both metabolic and anti-inflammatory effects, which may offer therapeutic benefits for psoriatic disease, particularly in the early stages of PsA. OBJECTIVES: This review aims to evaluate the current evidence on GLP-1RAs in PsO and PsA, examine the underlying pathophysiological mechanisms, and highlight key areas for future research, with a particular emphasis on early PsA as a critical window for intervention. METHODS: A narrative review in accordance with current methodological guidance was conducted on published studies concerning GLP-1RAs in PsO and PsA, including preclinical, clinical, and mechanistic research. RESULTS: Several studies show that GLP-1RAs, particularly liraglutide and semaglutide, improve PsO severity, metabolic parameters, and inflammatory markers. These benefits extend beyond weight loss, suggesting a direct immunomodulatory effect. Two open-label trials in PsA patients with obesity indicated improvements in disease activity (MDA) alongside metabolic benefits. The trials, NCT06588296 (TOGETHER-PsA) and NCT06864026 (TOGETHER AMPLIFY-PsA), assessed ixekizumab with and without tirzepatide. However, evidence in PsA remains limited, with most studies constrained by small sample sizes and short follow-up periods. To date, no studies have specifically investigated GLP-1RAs in early PsA; however, early-stage disease may represent an optimal treatment window for maximizing therapeutic effects based on immunometabolic rationale. CONCLUSIONS: GLP-1RAs show promising effects in PsO and early-PsA may represent a potential treatment window for maximizing therapeutic effects based on immunometabolic rationale, although this concept requires validation in dedicated clinical studies.