Diabetes is associated with an increased risk of kidney stones. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) might lower the risk of nephrolithiasis, as they increase urinary flow. However, a prior meta-analysis was inconclusive, and only one Danish study reported a lower risk of kidney stones. We investigated the association between SGLT2i use and the risk of nephrolithiasis in routine practice. Using claims data from 2 private health plans and Medicare (2013-2020) , we identified 331,028 pairs of 1:1 propensity score-matched adults with type 2 diabetes (T2D) initiating an SGLT2i or a DPP4 inhibitor (DPP4i) , and 358,203 pairs initiating an SGLT2i or a GLP1 receptor agonist (GLP1RA) . Our primary outcome was nephrolithiasis diagnosed by ICD codes in the inpatient or outpatient setting. We estimated hazard ratios (HRs) , rate differences (RD) and 95% confidence intervals (CI) , adjusting for 57 baseline covariates in the PS model. Over a mean follow-up of ∼months on treatment, the risk of nephrolithiasis was lower in the SGLT2i group compared with the DPP4i group (HR 0.74 [95%CI 0.71-0.77]; RD 4.0 [95%CI, -4.6, -3.4]) or the GLP1RA group (HR 0.69 [95%CI 0.67-0.72]; RD -4.1 [95%CI, -4.7, -3.5]) (Table) . Secondary definitions of the outcome based on a hospital discharge diagnosis produced consistent results. In routine care, SGLT2i use was associated with a reduced risk of nephrolithiasis, compared to DPP4i or GLP1RA use in patients with T2D.


J.M.Paik: None. H.Tesfaye: None. G.Curhan: Employee; OM1, Inc, Other Relationship; UpToDate. J.M.Mastrorilli: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

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