Clinical and mechanistic effects of GLP-1 receptor agonists in hidradenitis suppurativa and comorbidities

Hidradenitis suppurativa (HS) is a painful inflammatory skin disease within the pilosebaceous unit associated with numerous comorbidities, including obesity type-2-diabetes (T2DM), and a general meta-inflammatory state. This narrative review explores the therapeutic potential of GLP-1-receptor-agonists (GLP-1RAs) in treating HS by analyzing mechanisms of action and clinical outcomes. Based on a literature search, encompassing 12 cohorts and 4 case-based reports, current evidence demonstrates significant improvements in both clinical and patient-reported outcomes in patients with HS treated with GLP-1RAs. Treatment consistently resulted in reduced body mass index (BMI) and disease activity, 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 observed reductions in systemic inflammatory markers and improved glycemic control. The beneficial effects of GLP-1RAs in HS are attributed to the reduction in mechanical friction and metabolic improvements from weight loss. Suggestively, 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, 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. Four supplementary cohorts found GLP-1RAs beneficial for cardiovascular comorbidities in patients with HS. Additionally, studies suggest that GLP-1RAs enhance the efficacy of biologic therapies used for HS and reduce the need for adjunctive treatment. In conclusion, GLP-1RAs represent a promising pleiotropic treatment within a multimodal therapy strategy for HS and comorbidities.