Empagliflozin may reduce the risk of nephrolithiasis in patients with type 2 diabetes, according to new research presented at Kidney Week 2022, the annual meeting of the American Society of Nephrology, in Orlando, Florida.

Using 2013-2019 claims data from 2 private health plans and Medicare, investigators identified 102,275 pairs of matched adults with type 2 diabetes initiating empagliflozin (a sodium-glucose cotransporter-2 inhibitor; SGLT2i) or a dipeptidyl peptidase 4 inhibitor (DPP4i) and 115,489 pairs of matched adults initiating empagliflozin or a glucagon-like peptide 1 receptor agonist (GLP1RA).

Over a mean follow-up of approximately 8 months on treatment, the risk of a nephrolithiasis diagnosis was a significant 28% and 27% lower in the empagliflozin group compared with the DPP4i group and the GLP1RA group, respectively, Julie M. Paik, MD, ScD, MPH, of Brigham and Women’s Hospital in Boston, Massachusetts, reported on behalf of her team. In absolute terms, empagliflozin use was associated with 6.2 and 6.0 fewer stone cases per 1000 person years than DPP4i and GLP1RA use, respectively.

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“In routine care, empagliflozin use was associated with a reduced risk of nephrolithiasis,” Dr Paik told Renal & Urology News. “Clinicians might consider prescribing empagliflozin to patients with diabetes at higher risk of developing kidney stones who meet other indications for an SGLT2 inhibitor.”

She added, “Real-world evidence and randomized controlled trial data together can help advance our understanding of agents for stone prevention.”

Investigators from another study, published in The Journal of Clinical Endocrinology & Metabolism, reached similar conclusions based on data from randomized clinical trials. They pooled data from 20 phase I-IV trials involving 15,081 patients with type 2 diabetes randomly assigned to empagliflozin or placebo. Empagliflozin use was significantly associated with a 36% reduced risk of urolithiasis with 1.01 vs 0.63 urinary tract stone events occurring per 100 patient-years in the placebo vs empagliflozin group, respectively, Priyadarshini Balasubramanian, MD, of Yale School of Medicine in New Haven, Connecticut, and colleagues reported. The dose and median exposure of empagliflozin was 10 mg or 25 mg for 549 days.

“One proposed mechanism for decreased stone risk with SGLT2 inhibitors is increased urinary flow rate due to osmotic diuresis from glucosuria and natriuresis and consequent changes in urinary concentrations of lithogenic substances,” Dr Balasubramanian’s team wrote.

Disclosure: Both studies were supported by Boehringer Ingelheim Pharmaceuticals. Please see the original references for a full list of disclosures.


Paik JM, Tesfaye H, Zakoul H, et al. Empagliflozin use and the risk of nephrolithiasis in patients with type 2 diabetes. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract SA-PO259.

Balasubramanian P, Wanner C, Ferreira JP, et al. Empagliflozin and decreased risk of nephrolithiasis: A potential new role for SGLT2 inhibition? J Clin Endocrinol Metab. Published online June 16, 2022. doi:10.1210/clinem/dgac154