Glucagon-like peptide-1 receptor agonists in psoriasis management

Psoriasis is a chronic, systemic inflammatory skin disease associated with musculoskeletal, cardiovascular, metabolic, psychiatric, and gastrointestinal comorbidities. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists have emerged as potential therapeutic adjuncts for psoriasis because, beyond their metabolic effects, these agents exhibit anti-inflammatory properties and may reduce cytokine expression and inflammatory biomarkers. This review summarizes current evidence from randomized trials and nonrandomized studies on GLP-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists in patients with psoriasis and discusses their potential role in disease management. Observational studies of liraglutide, semaglutide, exenatide, dulaglutide, and tirzepatide generally showed improvements in psoriasis severity, body weight, metabolic parameters, inflammatory biomarkers, and quality of life, although most studies were limited by small sample sizes and uncontrolled designs. Randomized trials likewise suggest dermatologic benefit, particularly in patients with obesity, type 2 diabetes mellitus, or both. Most notably, the phase 3b TOGETHER trial demonstrated greater skin clearance and weight reduction with ixekizumab plus tirzepatide than with ixekizumab alone in patients with moderate-to-severe psoriasis and overweight or obesity. Complementary findings from the TOGETHER-Psoriatic Arthritis trial showed improvement in psoriatic arthritis disease activity as early as week four, before clinically meaningful weight loss, supporting the potential weight-independent anti-inflammatory effects of these agents. Future studies should include patients without obesity or diabetes to clarify the relative contributions of weight loss and direct anti-inflammatory effects to clinical response and determine whether the dermatologic benefits of GLP-1-based therapies extend to patients without underlying metabolic dysfunction.