Association of Pioglitazone Versus Dipeptidyl Peptidase-4 Inhibitor Use with Incident Gout in Type 2 Diabetes: a Real-World Cohort Study.

OBJECTIVE:Pioglitazone and dipeptidyl peptidase-4 inhibitors (DPP-4is) are used to treat type 2 diabetes mellitus (T2DM), yet their influence on gout risk remains unclear. This study aimed to examine whether the incidence of newly diagnosed gout differed between pioglitazone users and DPP-4i users among patients with T2DM. METHODS:We conducted a retrospective cohort study using data from the TriNetX. Patients with T2DM aged 20-84 years were selected. The pioglitazone and DPP-4i cohorts were matched 1:1 using propensity score matching based on demographic and clinical characteristics. The primary endpoint was incident gout. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the 'Compare Outcomes' module within the TriNetX. RESULTS:After propensity score matching and using post-matching 6-month lag exclusion, 120,095 patients in the pioglitazone group and 120,211 patients in the DPP-4i group were included. During the maximum follow-up period of 5 years, 1,948 cases of gout occurred in the pioglitazone group and 1,877 in the DPP-4i group, corresponding to cumulative incidence of 1.622% and 1.561%, respectively. The Cox proportional hazards analysis indicated a modestly higher incidence of gout among pioglitazone users compared with DPP-4i users (HR, 1.085; 95% CI, 1.018-1.156). CONCLUSION:Pioglitazone use is associated with a modestly higher incidence of gout compared with DPP-4i use in patients with T2DM; however, the small absolute risk difference and observational design warrant cautious interpretation.