Glucagon-like peptide-1 receptor agonists may improve psoriasis severity while also benefiting metabolic and inflammatory markers, according to a narrative review. However, evidence supporting their use in psoriatic arthritis remains limited, suggesting clinicians should view these findings as hypothesis-generating rather than practice-changing.
The review synthesized published preclinical, clinical, and mechanistic studies evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in psoriasis and psoriatic arthritis (PsA). Most of the available evidence involved patients with psoriasis and coexisting obesity, metabolic syndrome, or type 2 diabetes mellitus. Researchers assessed outcomes related to skin disease severity, inflammatory biomarkers, metabolic measures, and, where available, PsA disease activity.
Across the studies, liraglutide and semaglutide were associated with improvements in Psoriasis Area and Severity Index (PASI) scores, reductions in inflammatory markers, and improvements in metabolic measures. Several studies also reported histologic improvement in skin lesions and reductions in cytokines implicated in psoriatic disease, including interleukin (IL)-17, IL-23, tumor necrosis factor-alpha, IL-6, and C-reactive protein.
Among the clinical studies, a randomized controlled trial involving 25 patients with psoriasis and type 2 diabetes found that liraglutide was associated with greater improvement in PASI scores than conventional therapy and was accompanied by reduced expression of IL-17, IL-23, and tumor necrosis factor-alpha in skin tissue. Other prospective studies reviewed by the researchers reported improvements in psoriasis severity alongside reductions in body mass index, waist circumference, glycemic measures, and inflammatory biomarkers.
The researchers also noted evidence suggesting that some benefits may extend beyond weight loss alone. Several studies reported improvement in psoriasis severity before substantial weight reduction occurred or found that improvements were independent of the degree of weight loss, supporting a possible direct immunomodulatory effect in addition to metabolic benefits.
Evidence for semaglutide was similarly encouraging. In an open-label randomized trial involving 31 patients with psoriasis and type 2 diabetes, semaglutide was associated with reductions in PASI scores, serum IL-6 levels, and C-reactive protein compared with controls. A study described reductions in visceral adiposity and decreased epicardial inflammation on imaging studies alongside improvements in skin disease.
Evidence in PsA was considerably more limited. The review identified two open-label trials evaluating disease activity in patients with psoriatic arthritis and obesity, including a prospective study tracking 10 patients on liraglutide. After 3 months of treatment, investigators reported improvement in minimal disease activity as well as reductions in body mass index, waist circumference, glycemia, lipid levels, and C-reactive protein.
The review also highlighted ongoing clinical trials investigating tirzepatide in combination with ixekizumab in patients with active PsA and overweight or obesity. According to the researchers, these studies may help clarify whether targeting metabolic dysfunction alongside inflammation can improve joint and metabolic outcomes.
The current evidence has several important limitations. The review was narrative rather than systematic, and most included studies were small, observational, open-label, or case-based. Follow-up periods were generally short, and many participants had obesity and/or type 2 diabetes, which may limit generalizability to broader populations with psoriasis or PsA. The researchers also noted that distinguishing metabolic effects from direct immunomodulatory effects remains challenging.
Overall, the review concluded that GLP-1 RAs have shown encouraging results in psoriasis but require further study in PsA, particularly during earlier stages of disease. “Early-PsA may represent a potential treatment window for maximizing therapeutic effects based on immunometabolic rationale,” wrote lead study author Giovanni Ciancio, of the University of Modena and colleagues, while noting that the concept requires validation in dedicated clinical studies.
Disclosures: The researchers reported no funding for the work and declared no commercial or financial conflicts of interest.
Source: Frontiers in Immunology
