SGLT2 Inhibitors and Nephrolithiasis Risk in Adults With Type 2 Diabetes: A Systematic Review and Meta-analysis.
To evaluate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and nephrolithiasis in adults with type 2 diabetes.
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.
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.
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.
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.
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.
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.
Authors
Abreu Abreu, Santos Santos, Maalouf Maalouf, Sakhaee Sakhaee, Chiappa Chiappa
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