(219) A Description of Nephrolitiasis Associated with Sodium Glucose Co-Transporter 2 Inhibitors Use: A Vigibase Study

Publication Number: 1264

Background: Sodium-glucose cotransporter inhibitors (SGLT2i) treatment could lower the risk for incident and recurrent kidney stones in people with type 2 diabetes, as recent evidence suggests. However, a potential signal of neprolitiasis was also detected by the FDA a few years ago, in patients using SGLT2 inhibitors. It was also suggested that SGLT2i can cause hyperuricosuria, which may confer a greater risk for specific types of kidney stones.

Objectives: The objective of our study was to perform a descriptive analyses on nephrolitiasis cases reported to SGLT2i in the VigiBase®, in the scope of characterizing the patients and reactions, and to report on the disproportionality analysis.

Methods: We analyzed all nephrolitiasis reports for canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, and/or luseogliflozin from the VigiBase up to September 2021. Cases were reports containing Medical Dictionary for Regulatory Activities Preferred Terms (MedDRA PT) Nephrolithiasis. Gliflozin exposure was considered for all reports with at least one gliflozin as a suspected/ interacting drug. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR) for each of the gliflozins with both full database and antidiabetics reports only as backgrounds.

Results: Of the 27,370,413 total reports in VigiBase, we found 231 nephrolitiasis cases reported to gliflozins as suspected/ interacting drugs in 227 patients. The most cases with available information were reported in the region of the Americas, in the category of 45-64 years-of-age (60%) and male gender was more frequent (56%). Most of the reports were registered in 2015 (n=53) and came from spontaneous reporting/physicians. Almost all cases (except 2 reported to ertugliflozin and luseoglifozin) were reported to canagliflozin, dapagliflozin or empagliflozin alone or in combination with metformin or gliptins. The great majority of nephrolitiasis reports were serious (79%) and half (50% of the cases with this information available) had a favorable outcome. No fatal cases were reported. Data on the time-to-onset and reaction duration were too scarce for analysis. Disproportionality analysis showed a PRR ≥1 with ≥ 5 cases in 6 associations of nephrolitiasis and one of the gliflozins, with both full database (PRRs of 2.8-4.4) and antidiabetics reports only (PRRs of 1.8-2.9) as backgrounds.

Conclusions: SGLT2-inhibitors were associated with an increase in the proportion of reports of nephrolitiasis compared to other medications, according to disproportionality analysis in VigiBase®.