Anti-Inflammatory and Survival Benefits of Dipeptidyl Peptidase 4 Inhibitors Among Patients with Gout, T2DM Patients and Chronic Kidney Disease

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Abstract
Gout and type 2 diabetes mellitus (T2DM) often coexist and are associated with chronic kidney disease (CKD) and increased mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly used in T2DM, may offer additional benefits, such as reducing inflammation and uric acid levels. This study aimed to assess the impact of DPP-4 inhibitors on gout flare frequency, serum uric acid (sUA) levels, and survival in patients with gout, T2DM, and CKD.A cross-sectional, retrospective, longitudinal study was conducted over 6 years between 2016 – 2022, including patients with gout and T2DM from the largest healthcare provider in Israel. Patients were divided into treatment and control groups based on DPP4-inhibitor status treatment. The primary outcome was the number of gout arthritis attacks over 1 year, reflected by the number of emergency room visits. Secondary outcomes included mean serum high-sensitive C-reactive protein (hs-CRP) levels and survival rates over the study period.DPP-4 inhibitor treatment significantly reduced sUA levels (5.2±1.3 mg/dL vs. 5.9±2.2 mg/dL, p=0.05) and hs-CRP levels (0.50±0.19 mg/dL, p<0.001). Kaplan-Meier survival analysis suggested a trend towards improved survival in the DPP-4 inhibitor group (HR=0.834, 95% CI: 0.6–1.04, p=0.05), particularly among patients with chronic kidney disease (CKD), although without statistical significance. The emergency room visits due to gout attacks were fewer in the DPP-4 inhibitor group, although this difference did not achieve statistical significance.DPP-4 inhibitors may offer benefits beyond glycemic control in T2DM and gout, including reduced sUA and hs-CRP levels and improved survival in CKD patients. Larger, randomized trials are warranted to explore these potential benefits.

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