The National Psoriasis Foundation Primer on GLP-1 Receptor Agonists in Psoriasis

Importance: Psoriasis is a chronic immune-mediated disease associated with cardiovascular, metabolic, musculoskeletal, psychiatric, hepatic, kidney, and pulmonary comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved by the US Food and Drug Administration for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease, obstructive sleep apnea, and metabolic dysfunction-associated steatohepatitis-conditions common in psoriasis. Emerging evidence suggests GLP-1 RAs and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists may improve psoriatic skin disease, partly through immune modulation. If confirmed in larger randomized clinical trials, GLP-1-based therapies may offer an opportunity to address both cutaneous disease and cardiometabolic comorbidities. This primer from the US National Psoriasis Foundation Medical Board sought to provide an evidence-informed narrative synthesis and practical considerations to introduce dermatologists to GLP-1 RAs for psoriasis treatment. Observations: GLP-1 RAs have been associated with reductions in Psoriasis Area and Severity Index (PASI) scores, particularly in patients with obesity or type 2 diabetes. Studies report relative PASI reductions ranging from approximately 40% to 80% with parallel quality-of-life gains, although most of these studies are small (7-48 patients), short term (≤6 months), and lack a control group. Semaglutide and liraglutide have been associated with reductions in C-reactive protein, interleukin-6, lipids, and visceral adiposity. In small, translational cohorts, PASI improvement has been correlated with reductions in superficial adiposity and dermal γδ T-cell density. GLP-1 RAs combine safely with methotrexate, cyclosporine, and biologics. Adverse effects are mainly transient gastrointestinal symptoms; pancreatitis and gallbladder events are rare. Early data show both metabolic and immunomodulatory benefits. Conclusions and Relevance: This review found that GLP-1-based therapies target shared metabolic and inflammatory pathways in psoriasis. Current evidence supports consideration of adjunctive use in selected patients with metabolic comorbidities, although definitive conclusions await larger randomized clinical trials.