The Mechanism of Sodium-Glucose Cotransporter-2 Inhibitors in Reducing Uric Acid in Type 2 Diabetes Mellitus

Meiyuan Dong; Huiling Chen; Song Wen; Yue Yuan; Liling Yang; Dongxiang Xu; Ligang Zhou

doi:10.2147/DMSO.S399343

The Mechanism of Sodium-Glucose Cotransporter-2 Inhibitors in Reducing Uric Acid in Type 2 Diabetes Mellitus

Diabetes Metab Syndr Obes. 2023 Feb 14:16:437-445. doi: 10.2147/DMSO.S399343. eCollection 2023.

Authors

Meiyuan Dong^{1

2}, Huiling Chen², Song Wen², Yue Yuan², Liling Yang², Dongxiang Xu², Ligang Zhou^{1

2

3}

Affiliations

¹ Graduate School of Hebei Medical University, Shijiazhuang, People's Republic of China.
² Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People's Republic of China.
³ Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University, Shanghai, People's Republic of China.

Abstract

Hyperuricemia is a common comorbidity in patients with type 2 diabetes mellitus (T2DM), as insulin resistance (IR) or hyperinsulinemia is associated with higher serum uric acid (SUA) levels due to decreased uric acid (UA) secretion, and SUA vice versa is an important risk factor that promotes the occurrence and progression of T2DM and its complications. Growing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a novel anti-diabetic drug initially developed to treat T2DM, may exert favorable effects in reducing SUA. Currently, one of the possible mechanisms is that SGLT2i increases urinary glucose excretion, probably inhibiting glucose transport 9 (GLUT9)-mediated uric acid reabsorption in the collecting duct, resulting in increased uric acid excretion in exchange for glucose reabsorption. Regardless of this possible mechanism, the underlying comprehensive mechanisms remain poorly elucidated. Therefore, in the present review, a variety of other potential mechanisms will be covered to identify the therapeutic role of SGLT-2i in hyperuricemia.

Keywords: hyperuricemia; sodium-glucose cotransporter 2 inhibitors; type 2 diabetes mellitus; uric acid.

Publication types

Review

Grants and funding

This work was supported by the Project of Key Medical Discipline of Pudong Hospital of Fudan University (Zdxk2020-11), Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdzk2020-24), Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY- ZXYJHZX-2-201712), Special Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Pudong New Area Clinical Plateau Discipline Project (PWYgy-2021-03), the Natural Science Foundation of China (21675034), National Natural Science Foundation of China (81370932), Shanghai Natural Science Foundation (19ZR1447500), Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP0202118), and Education Funding in Wenzhou Medical University (JG2021197).