Empagliflozin and Decreased Risk of Nephrolithiasis: A Potential New Role for SGLT2 Inhibition?

Diabetes mellitus is a risk factor for nephrolithiasis. A recent observational study found that in patients with type 2 diabetes (T2D), SGLT2 inhibitor use was associated 49% lower of nephrolithiasis compared GLP-1 receptor agonists.
 Aim: we examined the association between and empagliflozin, using existing data from randomized clinical trials.
 Methods: pooled 15 081 T2D to empagliflozin (n = 10 177) or placebo 4904) 20 phase I-IV trials, including large cardiovascular outcome trial, EMPA-REG OUTCOME. Incident urinary tract stone events were captured predefined collection MedRA terms. sensitivity analysis narrower definition also performed. Incidence rate ratios (IRR) 95% CIs calculated relative estimate, stratified by study.
 Results: median exposures drug 543 days (placebo) 549 (empagliflozin); 183 experienced an incident urolithiasis during follow-up (placebo, 79; 104), yielding annual incidence rates 1.01 vs 0.63 events/100 patient-years respective groups. The IRR 0.64 (95% CI, 0.48-0.86), favor empagliflozin. In analysis, results similar (IRR, 0.62 [95% 0.45-0.85]).
 Conclusion: placebo, therapy approximate 40% reduced patients. underlying mechanisms are unknown but may involve altered lithogenic profile urine. Dedicated prospective trials warranted confirm these initial observations without T2D.