SGLT2 inhibitors and nephrolithiasis risk in patients with type 2 diabetes: A cohort study and meta-analysis.

AIMS

This study aimed to evaluate the relationship between sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and nephrolithiasis risk.

METHODS

In this real-world cohort study, we analyzed electronic health records from the TriNetX Analytics Network, which includes patients from 64 U.S. healthcare organizations. Adult patients with type 2 diabetes (T2D) who initiated SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP4is), or glucagon-like peptide-1 receptor agonists (GLP-1RAs) between January 2015 and December 2023 were included. Comparisons were made between SGLT2is and DPP4is and between SGLT2is and GLP-1RAs. Patients were followed-up for up to 5 years. A meta-analysis was further conducted to synthesize available evidence.

RESULTS

The cohort study included 500,000 patients (250,000 pairs) for SGLT2is vs. DPP4is comparisons and 482,284 patients (241,142 pairs) for SGLT2is vs. GLP-1Ras comparisons. The risk of nephrolithiasis was significantly lower in SGLT2i users compared with DPP4i (HR: 0.86; 95% CI: 0.83-0.90) and GLP-1RA users (HR: 0.90; 95% CI: 0.86-0.94). A meta-analysis combining our study with four additional real-world studies further supported these findings.

CONCLUSIONS

This study suggests that SGLT2is may provide benefits beyond glycemic control by reducing nephrolithiasis risk, offering an advantage when selecting glucose-lowering therapies for patients with T2D.