使用 SGLT2 抑制劑治療之第二型糖尿病患者的尿路結石發生率：台灣全國性世代研究

黎赫、周孟翰、曹智惟、蒙恩、查岱龍、孫光煥、于大雄

國防醫學大學三軍總醫院外科部泌尿外科

Incidence of urolithiasis in patients with type 2 diabetes treated with SGLT2 inhibitors: A nationwide cohort study in Taiwan

Ho Li, Meng-Han Chou, Chih-Wei Tsao, En Meng, Tai-Lung Cha, Guang-Huan Sun, Dah-Shyong Yu

Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan

Purpose: The association between sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and urinary stone formation remains unclear. While SGLT2i therapy provides established glycemic, cardiovascular, and renal benefits, its effect on nephrolithiasis in patients with type 2 diabetes mellitus (T2DM) has been inconsistent across studies. This study evaluated whether SGLT2i use is associated with a reduced risk of urinary stone formation and compared the relative effects of individual agents.

Materials and Methods: A retrospective cohort study was performed using the Taiwan National Health Insurance Research Database (2015–2017). Patients with T2DM were identified by ICD-9/10-CM codes, excluding those with prior urolithiasis. Users of SGLT2i (empagliflozin or dapagliflozin) were matched 1:4 with non-users by age, sex, and index year. The primary outcome was new-onset urinary stones. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional-hazards regression, adjusting for demographic factors, comorbidities, urbanization, and healthcare level. Follow-up continued until stone diagnosis, death, or the end of 2017. Ethical approval was obtained from the Tri-Service General Hospital Institutional Review Board (E202416030).

Results: A total of 10,345 patients were analyzed (2,069 SGLT2i users and 8,276 matched non-users). During a median follow-up of approximately 2.5 years, urinary stones occurred in 134 (6.48%) SGLT2i users and 811 (9.80%) non-users (P < 0.001). SGLT2i use was associated with a significantly lower risk of urolithiasis (aHR = 0.643, 95% CI 0.462–0.863, P < 0.001). In subgroup analyses, empagliflozin showed the strongest association with reduced risk (aHR = 0.615, 95% CI 0.433–0.827, P < 0.001), followed by dapagliflozin (aHR = 0.679, 95% CI 0.485–0.896, P < 0.001). The protective association remained consistent across subgroups stratified by age, sex, and comorbidities. Kaplan–Meier analysis showed a significantly lower cumulative incidence of urinary stones among SGLT2i users (log-rank P < 0.001).

Conclusions: In this nationwide cohort of patients with T2DM, SGLT2i use was associated with a 36% lower risk of urinary stone formation compared with non-use. Empagliflozin demonstrated the most prominent association with risk reduction. These findings support a possible class-related protective effect of SGLT2i on urolithiasis, consistent with previous population-based studies. Further prospective studies are warranted to confirm these associations and explore underlying mechanisms.