Heterogenous Effects of SGLT2 Inhibitors on Nephrolithiasis in Older Adults with Type 2 Diabetes

Mechanistic studies suggested that sodium-glucose cotransporter-2 inhibitors (SGLT2i) may reduce the risk of nephrolithiasis. We aimed to further assess this association using a real-world population of type 2 diabetes (T2D) patients. Among a 15% random sample of 2017-2018 Medicare fee-for-service beneficiaries with T2D, we identified new initiators of SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i). We followed the cohort until the first medical encounter with diagnosis of nephrolithiasis, death, or 12/31/2018. Inverse probability treatment weighting was used to balance the baseline covariates including sociodemographics, prior comorbidities and medications. Of 116,506 included individuals (age 72±10 years, 53% women), 0.96% developed nephrolithiasis over a median follow-up of 360 days. The crude incidence rate was 9.89 (95% confidence interval [CI] 8.49-11.52) and 11.02 (95% CI 10.34-11.73) per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i exposure was associated with a significantly lower risk of nephrolithiasis (hazard ratio 0.81 [95% CI 0.66-0.99]). This effect was more evident in men, non-Hispanic Black (NHB) individuals, and those without a history of nephrolithiasis. (Figure) SGLT2i was associated with a lower risk of nephrolithiasis, and the effect was more pronounced in men, NHB, and those without a history of nephrolithiasis. Disclosure Y.Li: None. H.Shao: Consultant; Lilly Diabetes. Y.Guo: None. Y.Zhang: None. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. L.Shi: None. J.Bian: None. A.G.Winterstein: Consultant; Bayer Inc., Genentech, Inc., Ipsen Biopharmaceuticals, Inc., Research Support; Merck Sharp & Dohme Corp. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.