GLP-1 Receptor Agonists significantly improve Hidradenitis Suppurativa symptoms and comorbidities via immunometabolic mechanisms

Hidradenitis suppurativa (HS) is a chronic, painful inflammatory skin disease affecting the pilosebaceous unit, often accompanied by severe comorbidities like obesity and type 2 diabetes (T2DM), contributing to a systemic meta-inflammatory state. Current treatments often fall short in addressing both the skin lesions and the associated metabolic dysfunction. Given the known anti-inflammatory and metabolic benefits of GLP-1 receptor agonists (GLP-1RAs) in other conditions, this review explores their potential as a pleiotropic therapeutic option for HS, targeting both disease activity and systemic comorbidities.

This narrative review synthesized findings from a literature search encompassing 12 cohorts and 4 case-based reports to evaluate the therapeutic potential of GLP-1 receptor agonists (GLP-1RAs) in treating Hidradenitis suppurativa (HS). The authors analyzed reported mechanisms of action and clinical outcomes across these studies. The primary focus was on assessing improvements in clinical and patient-reported outcomes, changes in metabolic markers, and evidence for direct anti-inflammatory effects independent of weight loss.

GLP-1 receptor agonists (GLP-1RAs) consistently demonstrated significant improvements in both clinical and patient-reported outcomes for patients with Hidradenitis suppurativa (HS). Treatment with GLP-1RAs led to reduced body mass index (BMI) and decreased disease activity, as measured by Hurley-staging and the number of nodules and abscesses. Patients across studies experienced fewer flares and less pain, supporting improvements in dermatology quality of life (DLQI) scores. Studies also observed reductions in systemic inflammatory markers and improved glycemic control. The beneficial effects are partly attributed to reduced mechanical friction and metabolic improvements from weight loss. > Crucially, concurrent and direct anti-inflammatory mechanisms, including inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and modulation of cytokines, appear to occur independently of weight-reduction. Results from cohorts and cases supported this theory, showing significant improvements in HS and metabolic markers independent of weight-related outcomes. Additionally, four supplementary cohorts found GLP-1RAs beneficial for cardiovascular comorbidities in patients with HS, and studies suggest GLP-1RAs enhance the efficacy of biologic therapies for HS, reducing the need for adjunctive treatment.