Abstract
Psoriasis is a systemic chronic inflammatory skin disease associated with musculoskeletal, cardiovascular, metabolic, psychiatric, and gastrointestinal comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs have emerged as potential therapeutic adjuncts in psoriasis because, beyond their metabolic effects, these agents exhibit anti-inflammatory properties and may reduce expression of cytokines and inflammatory biomarkers. This review summarizes the current evidence from randomized trials and nonrandomized studies evaluating GLP-1 RAs and dual GIP/GLP-1 RAs in patients with psoriasis and discusses their potential role in disease management. Observational studies of liraglutide, semaglutide, exenatide, dulaglutide, and tirzepatide generally demonstrated improvements in psoriasis severity, body weight, metabolic parameters, inflammatory biomarkers, and quality of life, although most were limited by small sample sizes and uncontrolled designs. Randomized trials similarly suggest dermatologic benefit, particularly among patients with obesity and/or type 2 diabetes mellitus. Most notably, the phase 3b TOGETHER trial demonstrated greater skin clearance and weight reduction with ixekizumab plus tirzepatide compared with ixekizumab alone in patients with moderate-to-severe psoriasis and overweight or obesity. Complementary findings from the TOGETHER-PsA trial showed improvement in psoriatic arthritis disease activity as early as week 4, before clinically meaningful weight loss, supporting 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.