Bridging Dermatology and Metabolic Medicine: The Role of GLP-1 Receptor Agonists in Psoriasis

In their manuscript, Vilarrassa et al. explore the bidirectional relationship between psoriasis, hidradenitis suppurativa (HS), and obesity. Given the pivotal role of obesity in fuelling inflammation in both PsO and HS, weight reduction has emerged as a fundamental therapeutic strategy. Studies have demonstrated that weight loss mitigates disease severity, enhances treatment response, and reduces cardiovascular risk in affected individuals. While lifestyle interventions such as diet and physical activity remain the cornerstone of weight management, adherence continues to pose a significant challenge, and bariatric surgery is not always a viable option. Against this backdrop, GLP-1 RAs, such as liraglutide and semaglutide, have gained prominence as promising therapeutic agents.

Studies have shown that liraglutide-induced weight loss correlates with improvements in Psoriasis Area and Severity Index (PASI) scores in psoriasis patients. One study involving seven obese patients with type 2 diabetes and psoriasis reported that a daily dose of liraglutide 1.2 mg for 10 weeks resulted in an average BMI reduction of 2 kg/m², alongside noticeable clinical improvement in psoriatic lesions. Another study involving three patients reported BMI reductions ranging from 0.8 to 3.8 kg/m² over 18 weeks, with a concurrent improvement in PASI scores. Although these sample sizes are small, the findings suggest that liraglutide may have a dual effect—facilitating weight loss while potentially alleviating psoriatic inflammation.

Semaglutide, a more potent GLP-1 RA with a longer half-life than liraglutide, has been associated with superior weight-loss outcomes. However, clinical data on its use in psoriasis remains limited. A case report described a 73-year-old patient with obesity, type 2 diabetes, and psoriasis who was treated with semaglutide 1 mg weekly for 10 months. The patient achieved a BMI reduction from 40.3 to 38.3 kg/m², with a notable improvement in psoriasis severity.

In a recent systematic review, tirzepatide, another member of this class of drugs, demonstrated more significant reductions in body weight and waist circumference compared to semaglutide. The placebo-adjusted weight reduction was 19.2% (95% CI: −22.2 to −16.2) with tirzepatide and 12.9% (95% CI: −14.7 to −11.1) with semaglutide. Similarly, the decrease in waist circumference was 14.6 cm (95% CI: −15.8 to −13.4) for tirzepatide and 9.7 cm (95% CI: −10.8 to −8.5) for semaglutide.

Although no data are currently available regarding its effects on psoriasis, tirzepatide may further enhance the therapeutic expectations for this class of drugs in addressing the metabolic disturbances associated with the disease.⁵

While the benefits of GLP-1 RAs in PsO and HS are largely attributed to weight loss, emerging evidence suggests that these agents may also exert direct anti-inflammatory effects. GLP-1 receptors are expressed on immune cells, including macrophages and dendritic cells, and their activation has been shown to attenuate systemic inflammation through modulation of nuclear factor kappa B (NF-κB) and inhibition of pro-inflammatory cytokine release. Preclinical studies further suggest that GLP-1 RAs may suppress Th17-mediated immune responses, a key driver of psoriasis pathogenesis.

The clinical application of GLP-1 receptor agonists has far exceeded its initial indication, now forming an integral part of pharmacological treatment in societies such as those in the Western world, where obesity affects between 10% and 20% of the population and up to 40% of individuals with psoriasis. However, despite representing an unprecedented therapeutic advancement, their limitations must also be acknowledged, including the potential for diminished efficacy over time and the risk of relapse. Additional questions remain regarding the sustainability of therapeutic benefits, potential disparities in response among psoriasis patients, and long-term safety and convenience, particularly gastrointestinal and cardiovascular effects.

In light of these considerations, dermatologists must adopt a more holistic approach to psoriasis management, recognizing obesity as a comorbidity and a key driver of disease pathogenesis. Future research should focus on elucidating the long-term benefits of GLP-1 receptor agonists in psoriasis and their potential synergistic effects with conventional immunomodulatory therapies.

By bridging the gap between dermatology and metabolic medicine, this article is a compelling call to action, urging clinicians to adopt an integrative perspective that acknowledges the intricate interplay between inflammation, metabolism, and immune dysfunction in psoriasis. Moreover, a multidisciplinary approach—encompassing dermatology, endocrinology, and metabolic medicine—could optimize patient outcomes by addressing systemic inflammation and metabolic dysregulation. And doing so may bring dermatologists closer to the realm of internal medicine—an area we should never entirely distance ourselves from.