The cardiovascular, renal, and cerebrovascular protective properties as well as metabolic benefits of SGLT2 inhibitors have been well established. However, the potential association between SGLT2 inhibitor treatment and the risk of kidney stones remains an area under investigation and discussion.

This study conducted a systematic search of PubMed, Embase, Cochrane Library, CNKI, and other Chinese and English databases (up to February 2025) and included 10 eligible studies involving 13,430,554 patients. A meta-analysis was performed to compare the risk of kidney stones between the SGLT-2 inhibitor group and the control group.

The results showed that the incidence of kidney stones in the SGLT-2 inhibitor group was significantly lower than that of the control group (odds ratio [OR]=0.68, 95% confidence interval [CI]: 0.57~0.82, P<0.01). Subgroup analysis further indicated that compared with the placebo group (OR=0.71, 95%CI: 0.56~0.90, P<0.01), the GLP-1RA group (OR=0.74, 95%CI: 0.57~0.97, P=0.03), and the DPP-4i group (OR=0.61, 95%CI: 0.40~0.95, P=0.03), SGLT-2 inhibitors were associated with a lower risk of kidney stones. Sensitivity analysis and publication bias tests supported the robustness of the results.

This study suggests that SGLT-2 inhibitors may reduce the risk of kidney stones, which has important implications for clinical practice in diabetic patients with hyperuricemia or a history of kidney stones. Future prospective studies are needed to verify the results, and the safety of their clinical application deserves further attention.