Effects of sodium-glucose co-transporter-2 inhibitors on the risk of nephrolithiasis and urinary tract infections in Thai patients with type 2 diabetes: a hospital-based cohort study

Abstract

Background: Nephrolithiasis is a multifactorial disease with many contributing factors varying across races, ethnicities, and sociocultural backgrounds. Diabetes is a significant independent risk factor for nephrolithiasis. We aimed to investigate the association between sodium-glucose co-transporter-2 inhibitors (SGLT2is) and the risk of nephrolithiasis in Thai patients with type 2 diabetes (T2D). Methods: This retrospective cohort study of T2D patients used real-world data from Ramathibodi Hospital, Bangkok, Thailand. Adult T2D patients aged 18 years or older who had received SGLT2is, dipeptidyl peptidase 4 inhibitors (DPP4is), sulfonylureas (SUs), or thiazolidinediones (TZDs) were included. Inverse probability weighting with regression adjustment and Cox proportional hazards models were applied to estimate the effect of SGLT2is on the risk of nephrolithiasis as the primary outcome, and on the risk of urinary tract infections (UTIs) as a secondary outcome. Results: A total of 17,821 patients were identified between 2015 and 2023, of whom 5,626 received an SGLT2i. The median follow-up time was 1.8 years. The incidence rate of nephrolithiasis was 7.7, 18.5, 20.5, and 12.1 per 1000 person-years in the SGLT2i, DPP4i, SU, and TZD groups, respectively. The risk of nephrolithiasis was significantly lower for patients who had received SGLT2is compared to those who had received DPP4is (HR = 0.45; 95% CI: 0.35, 0.58), SUs (HR = 0.37; 95% CI: 0.28, 0.48), and TZDs (HR = 0.60; 95% CI: 0.43, 0.85). The risk of UTIs appeared lower with SGLT2is compared to DPP4is (HR = 0.85; 95% CI: 0.66, 1.10) and TZDs (HR = 0.78; 95% CI: 0.55, 1.11), with a statistically significant reduction observed only relative to SUs (HR = 0.74; 95% CI: 0.56, 0.96). Conclusions: Our real-world study suggested a lower risk of nephrolithiasis in Thai T2D patients treated with SGLT2is, without any increase in UTIs. These real-world findings identify added benefit for T2D patients prescribed SGLT2is for nephrolithiasis prevention.