Empagliflozin Use Could Reduce Risk of Kidney Stones in T2D

Priyadarshini Balasubramanian, MD

With every passing conference in endocrinology, clinicians are offered the opportunity to learn about another benefit of SGLT2 inhibitor use.

At the Endocrine Society’s annual meeting (ENDO 2022), a new analysis of data from more than a dozen randomized, placebo-controlled trials suggest use of empagliflozin in patients with type 2 diabetes was associated with a 36% reduction in the incidence rate of kidney stones.

“Compared with placebo, treatment with empagliflozin was associated with an approximate 40% reduced risk of kidney stones in type 2 diabetes patients,” said lead researcher Priyadarshini Balasubramanian, MD, of the Yale School of Medicine in New Haven, Conn, in a statement. “While we do not know the precise mechanism underlying this benefit, the findings mean that empagliflozin may be used to prevent kidney stones in individuals with type 2 diabetes.”

Thanks to a multitude of clinical trials and other studies, knowledge of the cardiorenal protective benefit provided by SGLT2 inhibitors for patients with type 2 diabetes have become well-established in recent years. As further data from these studies emerge, clinicians are offered the opportunity to learn more about the impact of these agents on the overall health of patients. Spurred by a recent observational study suggesting use of SGLT2 inhibitors reduced risk of nephrolithiasis in patients with type 2 diabetes when compared to GLP-1 receptor agonists, Balasubramanian and a team of colleagues from institutions in Europe and Canada sought to assess the potential risk reduction provided by empagliflozin using data from randomized clinical trials.

After a search, investigators had identified 20 phase 1-4 randomized, placebo-controlled trials with pooled data from 15,081 patients for inclusion in their analyses. Of the 15,081 patients included, 10,177 received empagliflozin and 4904 received placebo therapy; these groups had a median time of exposure to study drug of 549 and 543 days, respectively. For the purpose of analysis, investigators assessed incident urinary tract stone events using a predefined collection of MedDRA codes, including nephrolithiasis, renal colic, ureterolithiasis, calculus bladder, calculus urinary, calculus urethral, and nephrocalcinosis.

Upon analysis, investigators identified 183 incident urolithiasis events during follow-up, with 79 occurring in the placebo group and 104 in the pooled empagliflozin group, which correlates to annual incident rates of 1.01 and 0.63 events per 100 patient-years, respectively. Investigators also pointed out all but 1 event occurred in patients with no prior history of urinary tract stones.

Further analysis indicated the incidence rate ratio for urinary tract stones was 0.64 (95% CI, 0.48-0.86) for empagliflozin use compared against placebo therapy. Investigators noted similar results were observed in a sensitivity analysis that was restricted to nephrolithiasis, ureterolithiasis, calculus bladder, calculus urinary, and calculus urethral (IRR, 0.62 [95% CI, 0.45-0.85]).

“Based on these initial observations, mechanistic studies to elucidate the mediator(s) of this seemingly protective effect and dedicated randomized prospective clinical trials appear warranted in patients with renal stone disease. As with follow-up SGLT2 inhibitor investigations conducted in patients with heart failure and chronic kidney disease, such trials should include individuals who do not have T2D,” wrote investigators.

This study, “Empagliflozin and the Risk of Nephrolithiasis,” was presented at ENDO 2022.