Empagliflozin lowers risk for kidney stones in type 2 diabetes
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ATLANTA — Use of empagliflozin was associated with a nearly 40% reduced risk for nephrolithiasis among people with type 2 diabetes, according to data presented at ENDO 2022.
“Diabetes is a well-known risk factor for nephrolithiasis,” Priyadarshini Balasubramanian, MD, a clinical fellow in diabetes, endocrinology and metabolism at the Yale School of Medicine, told Healio. “SGLT2 inhibitors, in addition to their many other benefits, may someday also be used to decrease the risk of kidney stones — at least in those with type 2 diabetes, but maybe also in those without diabetes.”
Balasubramanian and colleagues analyzed data from 15,081 adults who participated in 20 randomized placebo-controlled trials. Of the study cohort, 10,177 were treated with 10 mg or 25 mg empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly), and 4,904 received placebo. Incident urinary tract stone events were collected using a series of terms, including nephrolithiasis, renal colic, ureterolithiasis, calculus bladder, calculus urinary, calculus urethral and nephrocalcinosis. Incidence rate ratios (IRRs) were calculated using the relative risk estimate stratified from the data.
The median time of exposure was 549 days for the empagliflozin group and 543 days for placebo. Of the study cohort, 183 had an incident urinary tract stone event, including 104 using empagliflozin and 79 using placebo. The annual IRRs were 0.63 per 100 patient-years for the empagliflozin group and 1.01 per 100 patient-years for placebo. Adults using empagliflozin had a lower IRR for incident nephrolithiasis compared with placebo (IRR = 0.64; 95% CI, 0.48-0.86).
Balasubramanian said there are several possible mechanisms that may explain why people using empagliflozin have fewer incidences of nephrolithiasis.
“SGLT2 inhibitors are associated with increased urinary flow and dilution of lithogenic substances in the urine,” Balasubramanian said. “Several studies have shown at least short-term increase in urinary volumes from SGLT2 inhibition. Another potential mechanism is an increase in urinary citrate, which serves to inhibit supersaturation of calcium phosphate salts. Overall risk of calcium oxalate stones might also be decreased due to decrease in supersaturation of calcium phosphate. A recent post hoc analysis demonstrated an increase in urinary citrate excretion with the use of empagliflozin. However, SGLT2 inhibitors are associated with an increase in urate excretion, which could actually increase the risk of urate stones. Animal experiments have shown increased bicarbonate excretion after SGLT2 inhibition. Increased urinary bicarbonate might provide an alkaline milieu and thus may still prevent stone formation even in patients with high urinary urate.”
Balasubramanian said randomized prospective clinical trials are needed to confirm the findings. Studies on the lithogenic profile of the urine in stone formers after SGLT2 inhibitor use should also be conducted to provide data on the underlying mechanisms.
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Balasubramanian P, et al. PSUN155. Presented at: ENDO Annual Meeting; June 11-14, 2022; Atlanta (hybrid meeting).
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