SGLT2 Inhibitors and Nephrolithiasis Risk in Adults With Type 2 Diabetes: A Systematic Review and Meta-analysis.

Abstract

Objective: To evaluate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and nephrolithiasis in adults with type 2 diabetes.

Methods: We searched PubMed, Embase, and CENTRAL through April 26, 2026, for comparative studies of SGLT2i in adults with type 2 diabetes. We pooled comparison-level effect estimates using restricted maximum likelihood random-effects models and reported summary odds ratios (ORs). We assessed heterogeneity with I² and 95% prediction intervals, performed subgroup analyses and meta-regression, and assessed risk of bias.

Results: We included 10 studies, contributing 14 comparisons. SGLT2i were associated with lower odds of nephrolithiasis across all comparators (OR 0.72, 95% CI 0.65-0.80; p < 0.001; I² = 97.5%; 95% prediction interval 0.48-1.08). The association was strongest versus non-user controls (OR 0.55, 95% CI 0.52-0.58), followed by placebo (OR 0.65, 95% CI 0.49-0.85), DPP-4 inhibitors (OR 0.74, 95% CI 0.63-0.86), and glucagon-like peptide-1 receptor agonists (OR 0.79, 95% CI 0.70-0.90) (p for subgroup difference < 0.0001). Associations were consistent across study designs; outcome ascertainment methods did not significantly modify the association. Comparator class accounted for 29.5% of between-comparison variability, although the moderator test was not statistically significant (p = 0.10); follow-up duration was not significantly associated with effect size.

Conclusion: SGLT2i were associated with lower odds of nephrolithiasis in adults with type 2 diabetes. Substantial heterogeneity and the largely observational evidence base limit causal interpretation. Future studies should use adjudicated stone outcomes and urinary biochemical data.