Comparative Risk of Kidney Stone Formation Between SGLT2 Inhibitors and DPP-4 Inhibitors in Diabetic Patients : Systematic review and Meta-Analysis
Keywords:
SGLT2 inhibitors, DPP-4 inhibitors, nephrolithiasis, type 2 diabetes mellitusAbstract
Background: Patients with type 2 diabetes face a significantly higher risk of nephrolithiasis, which often results in frequent recurrences and substantial healthcare burdens. Sodium–glucose cotransporter-2 (SGLT2) inhibitors may offer lithoprotective benefits through osmotic diuresis and altered urinary composition. This meta-analysis evaluates the association between SGLT2 inhibitor use and nephrolithiasis incidence or recurrence compared with dipeptidyl peptidase-4 inhibitors.
Methods: Following PRISMA guidelines, a systematic literature search was performed in PubMed, Scopus, Europe PMC, and EBSCOhost up to June 2026 to identify studies comparing SGLT2 inhibitors and DPP-4 inhibitors regarding nephrolithiasis outcomes. Quality assessment was conducted using ROBINS-I. Pooled effect estimates were calculated as Hazard Ratios (HRs) or Incidence Rate Ratios (IRRs) with 95% confidence intervals (CIs) using a random-effects model in RevMan 5.4
Results: Seven retrospective cohort studies involving more than 2 million participants met the inclusion criteria. Five studies evaluating incident nephrolithiasis demonstrated that SGLT2i were associated with a significantly lower risk than DPP-4i (pooled HR = 0.68, 95% CI: 0.59–0.79; p < 0.00001), although substantial heterogeneity was observed (I² = 97%). Three studies assessing recurrent nephrolithiasis also showed a significantly reduced recurrence rate among SGLT2i users (pooled RR = 0.79, 95% CI: 0.65–0.98; p = 0.03), with considerable heterogeneity (I² = 97%). Risk of bias assessment indicated an overall moderate methodological quality, with residual confounding representing the primary source of bias.
Conclusion: Compared with DPP-4 inhibitors, SGLT2 inhibitors were consistently associated with a reduced risk of both incident and recurrent nephrolithiasis in patients with T2DM.
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Copyright (c) 2026 Mohamad Shadam, Ghufran Jabbar Maulana, Hussam Hilal Alkatiry, Abubakar Jamal Alweini, Reza Pratama, Satria Adji Hady Prabowo (Author)
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