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Empagliflozin and decreased risk of nephrolithiasis: A potential new role for SGLT2 inhibition?

Abstract : Aims Diabetes mellitus is a risk factor for nephrolithiasis. A recent observational study found that SGLT2 inhibitor use by type 2 diabetes (T2D) patients was associated with a 49% lower risk of nephrolithiasis, compared to GLP-1 receptor agonists. We examined the association between nephrolithiasis and the SGLT2 inhibitor empagliflozin, using existing data from randomized clinical trials. Methods We pooled data from 15,081 T2D patients randomized to empagliflozin (n=10,177) or placebo (n=4,904) from 20 phase I-IV trials including the large CV outcome trial, EMPA-REG OUTCOME. Incident urinary tract stone events were captured using a pre-defined collection of MedRA terms. A sensitivity analysis using a narrower definition was also performed. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated using the relative risk estimate, stratified by study. Results The median exposures to study drug was 543 days (placebo) and 549 days (empagliflozin).183 patients experienced an incident urolithiasis during follow-up (placebo, 79; empagliflozin,104), yielding annual incidence rates of 1.01 versus 0.63 events/100 patient-years in the two respective groups. The IRR was 0.64 (95% CI 0.48, 0.86), in favor of empagliflozin. In the sensitivity analysis, the results were similar (IRR, 0.62 [95% CI 0.45, 0.85]). Conclusion Compared to placebo, empagliflozin therapy was associated with an approximate 40% reduced risk of urinary tract stone events in T2D patients. The underlying mechanisms are unknown but may involve altered lithogenic profile of the urine. Dedicated randomized prospective clinical trials are warranted to confirm these initial observations in both patients with and without T2D.
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https://hal.univ-lorraine.fr/hal-03613635
Contributor : Erwan Bozec Connect in order to contact the contributor
Submitted on : Friday, March 18, 2022 - 4:02:07 PM
Last modification on : Friday, March 25, 2022 - 6:30:03 PM

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Priyadarshini Balasubramanian, Christoph Wanner, João Pedro Ferreira, Anne Pernille Ofstad, Amelie Elsaesser, et al.. Empagliflozin and decreased risk of nephrolithiasis: A potential new role for SGLT2 inhibition?. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2022, pp.dgac154. ⟨10.1210/clinem/dgac154⟩. ⟨hal-03613635⟩

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