Targeting Metainflammation in Hidradenitis Suppurativa: The Emerging Role of GLP-1 Receptor Agonists and Metabolic Pharmacotherapies

Hidradenitis suppurativa (HS) is a systemic inflammatory skin disease associated with obesity, insulin resistance, and visceral adiposity. Chronic metainflammation may contribute to cutaneous disease activity, while metabolic dysregulation potentially occurs independently of body mass index (BMI). Additionally, emerging metabolic pharmacotherapies may provide weight-dependent and weight-independent immunomodulatory benefits in HS. This narrative review synthesizes clinical and mechanistic evidence for glucagon-like peptide-1 receptor agonists (GLP-1RAs), GLP-1RA multi-agonists, metformin, sodium–glucose cotransporter 2 inhibitors (SGLT-2is), and peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists in HS management. A structured PubMed and Embase search (28 March 2026) identified key metabolic–inflammatory targets. Proposed mechanisms include adipokine axis modulation (increased adiponectin; reduced leptin, retinol-binding protein 4, and haptoglobin); inhibition of nuclear factor kappa B (NF-κB) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling; restoration of cutaneous antimicrobial peptides; and improved gut barrier function. Early screening for metabolic syndrome (MetS) enables dermatologists to initiate targeted metabolic pharmacotherapy before irreversible cutaneous scarring occurs. Integrating metabolic therapies into HS treatment algorithms using metabolic and inflammatory biomarkers supports phenotype-driven care, offering a synergistic strategy to optimize cutaneous control, extend biologic drug survival, and improve cardiometabolic health in selected patients with HS.