Use of Sodium-Glucose Transport Protein 2 Inhibitors and the Incidence of Urolithiasis: A Multi-Database and Cross-Country Study in Patients With Type 2 Diabetes Mellitus

Abstract

The benefits of sodium-glucose transport protein 2 inhibitor (SGLT2i) use on severe urolithiasis requiring surgery remains unclear. All patients with incident T2D in Taiwan National Health Institution databases (2016-2021) and TriNetX datasets (2014-2023) were retrospectively analyzed. The study analyzed a propensity score-matched pairs with T2D treated with SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i). The primary outcome was the incidence of urolithiasis and urolithiasis requiring surgery during the study period. Urolithiasis diagnoses were identified using International Classification of Diseases diagnostic codes and categorized into upper and lower urinary tract stones. Cases of urolithiasis requiring surgery were determined by the presence of both diagnostic codes and surgical procedure codes within the same outpatient visit or hospitalization. Conditional and time-dependent Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the study period, 5700 participants were diagnosed with urolithiasis, 1297 participants were urolithiasis requiring surgery in Taiwan NHIRD cohort 8438 participants with urolithiasis as well as 289 participants with urolithiasis requiring surgery were in the TriNetX cohort. Adjusted HRs of urolithiasis and urolithiasis requiring surgery were 0.82-fold (95% CI, 0.77-0.87), 0.72-fold (95% CI, 0.63-0.82) in Taiwan NHIRD, 0.84 (95% CI, 0.78-0.90), and 0.62 (95% CI, 0.44-0.88) in TriNetX cohort respectively. Similar protective associations with SGLT2i use against urolithiasis were observed across subgroups in both datasets from Taiwan NHIRD and TriNetX. In conclusion, SGLT2i might protect against kidney stones and severe cases requiring surgery in T2D patients.

Figure 1

Flow diagram of the study patient selection.

Figure 2

Cumulative incidence of urolithiasis and urolithiasis requiring surgery among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors or DPP‐4 inhibitors. Kaplan–Meier curves showing the cumulative incidence of (a) urolithiasis and (c) urolithiasis requiring surgery in the Taiwan National Health Insurance Research Database cohort, and (b) urolithiasis and (d) urolithiasis requiring surgery in the TriNetX cohort. DPP‐4i, dipeptidyl peptidase‐4 inhibitors; SGLT2i, sodium‐glucose cotransporter‐2 inhibitors.

Figure 3

Associations between SGLT2i use and urolithiasis in different locations using conditional Cox regression models.