Molecular insights into GLP-1 receptor agonists and emerging metabolic-inflammatory targets in hidradenitis...

Hidradenitis suppurativa (HS) is increasingly recognized as a systemic immunometabolic disease associated with obesity, insulin resistance, and metabolic syndrome (MetS). A metabolically unhealthy lean phenotype indicates that metabolic dysfunction and chronic low-grade inflammation may occur independently of increased body mass index (BMI) in patients with HS. Reduced effectiveness of biologic therapies in patients with obesity further supports targeting the upstream metabolic drivers of inflammation.

This review outlines metabolic-inflammatory pathways proposed to contribute to HS, including insulin/insulin-like growth factor 1 (IGF-1) signaling, mechanistic target of rapamycin complex 1 (mTORC1) overactivation, adipokine dysregulation, and gut-skin interactions. Building on this framework, this review evaluates evidence on glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual incretin agonists, and other metabolic interventions, including metformin is evaluated.

GLP-1RAs may serve as adjunctive metabolic therapies for selected patients with HS and obesity or MetS. By promoting weight loss and metabolic improvement, they may reduce systemic inflammation, perioperative risk, and improve responses to weight-based biologics. However, current evidence remains mainly observational and is confounded by concomitant therapies. Randomized controlled trials using well-defined dermatological and metabolic endpoints are needed before routine implementation.