SGLT2 Inhibitors Cut Psoriatic Arthritis Risk by 20% Compared to GLP-1 RAs in T2DM

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease often co-occurring with type 2 diabetes mellitus (T2DM), increasing patients' risk of cardiovascular events and negatively impacting quality of life. Current T2DM treatments, such as SGLT2 inhibitors and GLP-1 receptor agonists, offer metabolic benefits and some anti-inflammatory properties. However, their comparative effects on the incidence of PsA in T2DM patients have remained unclear, representing a critical gap in optimizing treatment strategies for this high-risk population.

This emulated target trial compared incident PsA risk in 188,378 SGLT2 inhibitor users and 213,218 GLP-1 receptor agonist users from the TriNetX network (2016-2024). After propensity score matching, 146,810 matched pairs were analyzed. The primary outcome was incident PsA, with Kaplan-Meier analysis used to estimate outcome probabilities and hazard ratios (HRs) calculated to compare treatment strategies. Sensitivity analyses confirmed the findings.

SGLT2 inhibitor users demonstrated a significantly lower risk of developing PsA compared to GLP-1 receptor agonist users, with a hazard ratio of 0.793 (95% CI, 0.667-0.944) at 5 years of follow-up. This indicates a 20.7% reduction in PsA risk. The proportional hazards assumption was met (p > 0.05), supporting the validity of the HR calculation. Kaplan-Meier curves further revealed a significantly lower cumulative incidence of PsA among SGLT2i users (Log rank test p = 0.008). These associations remained robust even after adjusting for multiple covariates and were consistently supported by per-protocol sensitivity analyses, reinforcing the observed protective effect of SGLT2 inhibitors against PsA development in T2DM patients.