Psychiatric Outcomes After GLP-1 Receptor Agonists vs Metformin in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with obesity and psychiatric comorbidity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin are commonly prescribed for metabolic disease, but reports have raised concerns regarding potential psychiatric adverse effects of GLP-1RAs. We evaluated psychiatric outcomes following GLP-1RA versus metformin initiation among adults with HS. We conducted a retrospective cohort study within the NIH All of Us Research Program (Controlled Tier v8) using a new-user, active-comparator design. Adults with HS were identified using SNOMED concepts. Incident GLP-1RA users were compared with incident metformin users after a 365-day washout. The primary outcome was the first psychiatric diagnosis within 12 months of treatment initiation. Confounding was addressed using stabilized inverse probability of treatment weighting. The weighted analytic cohort included 76.7 GLP-1RA users and 232.5 metformin users. At 12 months, psychiatric diagnoses occurred in 61.3% of GLP-1RA users versus 51.1% of metformin users (risk difference +10.2 percentage points; risk ratio 1.20; 95% CI 0.95–1.52). The hazard ratio for time to first psychiatric diagnosis was 1.26 (95% CI 0.90–1.78), with divergence occurring early after initiation. Among adults with HS, GLP-1RA initiation was associated with a modest, nonsignificant increase in psychiatric diagnoses compared with metformin. These findings are hypothesis-generating and warrant further investigation.