Comparative Risk of Psoriatic Arthritis in Type 2 Diabetes: An Emulated Target Trial of SGLT2 Inhibitors vs. GLP-1 Receptor Agonists
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Background Patients with psoriatic arthritis (PsA) have a higher prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular events. They also experience increased absenteeism and reduced work productivity, all of which can negatively affect both life expectancy and quality of life. Objective We conducted this emulated target trial to compare the risk of incident PsA among patients with T2DM treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus those treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA). Methods We identified 188,378 users of SGLT2 inhibitors and 213,218 users of GLP-1 receptor agonists within the TriNetX network between January 1, 2016, and December 31, 2024. Following propensity score matching, 146,810 matched pairs of SGLT2i and GLP-1 RA users were included for analysis. The primary causal estimands were the intention-to-treat (ITT) effects of the respective treatment strategies. Kaplan–Meier analysis was employed to estimate outcome probabilities, and hazard ratios (HRs) with corresponding confidence intervals (CIs) were calculated, along with tests for proportionality. Results In this emulated target trial, users of SGLT2i showed a significantly lower risk of developing PsA compared to users of GLP-1 RA. At 5 years of follow-up, the hazard ratio for PsA was 0.793 (95% CI, 0.667–0.944). The proportional hazards assumption was tested and met (p > 0.05). Kaplan–Meier curves further showed a significantly lower cumulative in
Abstract
Background Patients with psoriatic arthritis (PsA) have a higher prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular events. They also experience increased absenteeism and reduced work productivity, all of which can negatively affect both life expectancy and quality of life. Objective We conducted this emulated target trial to compare the risk of incident PsA among patients with T2DM treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus those treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA). Methods We identified 188,378 users of SGLT2 inhibitors and 213,218 users of GLP-1 receptor agonists within the TriNetX network between January 1, 2016, and December 31, 2024. Following propensity score matching, 146,810 matched pairs of SGLT2i and GLP-1 RA users were included for analysis. The primary causal estimands were the intention-to-treat (ITT) effects of the respective treatment strategies. Kaplan–Meier analysis was employed to estimate outcome probabilities, and hazard ratios (HRs) with corresponding confidence intervals (CIs) were calculated, along with tests for proportionality. Results In this emulated target trial, users of SGLT2i showed a significantly lower risk of developing PsA compared to users of GLP-1 RA. At 5 years of follow-up, the hazard ratio for PsA was 0.793 (95% CI, 0.667–0.944). The proportional hazards assumption was tested and met (p > 0.05). Kaplan–Meier curves further showed a significantly lower cumulative incidence of PsA among SGLT2i users compared to GLP-1 RA users (Log rank test p = 0.008). These associations remained consistent after adjusting for multiple covariates and were further supported by sensitivity analyses using a per-protocol approach. Conclusion This multicenter emulated target trial found that SGLT2i use was associated with a lower risk of incident PsA compared with GLP-1 RA use. However, given the observational nature of the study and the potential for residual confounding despite extensive adjustment, these findings should be interpreted with caution. Further prospective and randomized studies are warranted to confirm this association.