Abstract Disclosure: R.K. Shariff: None. C. Chung: None. P. Huang: None. S. Mon: None. K. Ma: None. Background/Purpose: Effective management of gout in patients requiring long-term urate-lowering therapy involves maintaining serum rate levels within specific ranges. Hyperuricemia and gout have been associated with an increased risk of Type 2 Diabetes Mellitus (T2DM), with a reported prevalence of 16% in gout patients. Pharmacological approaches to glycemic control, including Sodium-glucose Transport Protein 2 Inhibitors inhibitor (SGLT2i) and Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), have showed potential serum urate lowering effects. However, a direct comparison of these effects in patients with gout and concomitant T2DM is lacking. This study aims to evaluate the serum urate-lowering effects of SGLT2i compared to DPP-4i in this patient population. Methods: This was a population-based cohort study of patients with gout diagnosed following the 2015 Gout classification criteria in the American College of Rheumatology/European League Against Rheumatism collaborative initiative and T2DM diagnosed following the American Diabetes Association criteria, respectively. Subjects treated between 2008 and 2023 at 92 United States hospitals were screened. Propensity score matching was used to balance the baseline differences in age of gout onset, sex, comorbidities, and past medical history between the two groups. The primary predictor variable was the use of therapies of SGLT2i and DPP-4i. The primary outcome of interest was the serum urate more than 6 mg/dL during the follow-up period. Kaplan-Meier analysis and log-rank tests were utilized to compare if the numbers of serum urate were higher than 6 mg/dL in both arms. A Cox proportional hazards model was utilized to estimate the association between the use of SGLT2i versus DPP-4i and the numbers of serum urate higher than 6 mg/dL. Inclusion criteria include patients with gout and concomitant T2DM, age over 18, and must have serum uric acid level data available. Results: Of the 11,495 gout patients, including 3,593 users of SGLT2i users, were propensity score-matched to 3593 DPP-4i users. Among gout patients with T2DM on SGLT2i, 598 experienced serum urate levels exceeding than 6 mg/dL, while in the DPP-4i group, 920 patients had serum urate higher than 6 mg/dL. The use of SGLT2i was associated with significantly lower odds of serum uric acid exceeding 6 mg/dl compared to DPP-4i. (OR: 0.580 [0.517-0.651]). Conclusion: Our study suggests that SGLT2i may offer a more effective means of managing serum uric acid levels in gout patients with concomitant T2DM compared to DPP-4i. Clinical trials are required to validate the findings. For clinical practice, the dosage for SGLT2i to cause the urate-lowering effect needs to be investigated. With further studies and clinical trials, the rationale of choosing SGLT2i over DPP-4i may be incorporated into the management of T2DM in gout patients with T2DM. Presentation: 6/1/2024