Psychiatric Outcomes after GLP-1 Receptor Agonists versus Metformin in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with obesity and a high burden of psychiatric comorbidity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin are commonly prescribed for metabolic disease and have anti-inflammatory effects, prompting interest in their use among patients with HS. However, recent 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 validated SNOMED concepts. Incident users of GLP-1RAs were compared with incident users of metformin after a 365-day washout. The primary outcome was the first psychiatric diagnosis within 12 months of treatment initiation. Stabilized inverse probability of treatment weighting (IPTW) was used to control for confounding. Effect estimates included 12-month cumulative risks, risk differences (RD), risk ratios (RR), and IPTW-weighted Cox proportional hazards models.

The weighted analytic cohort included 77 GLP-1RA users and 233 metformin users. At 12 months, psychiatric diagnoses occurred in 61.3% of GLP-1RA users versus 51.1% of metformin users (RD + 10.2 percentage points; RR 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). Divergence between groups occurred primarily within the first 90 days 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.