Association of kidney function with SGLT2 inhibitor discontinuation among United States Veterans.

Background: The impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on cardiovascular disease and chronic kidney disease (CKD) may be limited if discontinued in persons with CKD. We sought to determine whether CKD at SGLT2i initiation was associated with subsequent discontinuation.

Methods: This cohort study used electronic health record data of patients who initiated SGLT2i in the Veterans Health Administration from January 2017 through December 2021. The primary exposure was eGFR category at the time of SGLT2i initiation. The risk of SGLT2i discontinuation, defined by a provider order or expiration of an SGLT2i prescription without resumption in the following 180 days, was estimated using proportional hazards models with inverse probability weights for censoring due to death. Analyses were stratified by year of SGLT2i initiation.

Results: Among the 222,772 patients initiating an SGLT2i during the study period, median age was 68 (IQR: 60-73) years, 95% were male, and median (IQR) eGFR was 73 (58, 89) mL/min/1.73m2. Median follow-up was 1.6 years; 32% experienced SGLT2i discontinuation. Cumulative risk of discontinuation at one year was 21% to 27% across calendar years; approximately 41% of these discontinuations occurred within the first three months. There was a graded association between lower baseline eGFR and greater risk of discontinuation; this association attenuated across calendar years. Those initiating an SGLT2i in 2017 with baseline eGFR of 45-59 and 30-44 had 1.34- (95%CI: 1.21-1.49) and 2.04-fold (95%CI: 1.58-2.63) risks of discontinuation, respectively, compared to those with eGFR ≥60 ml/min/1.73m2. These hazard ratios reduced to 1.05 (95%CI: 1.02-1.10) and 1.20 (95%CI: 1.14-1.26), respectively, in those initiated in 2021.

Conclusions: A substantial proportion of patients experience SGLT2i discontinuation within a year of initiation. Persons with lower eGFR had higher discontinuation rates; however, this trend attenuated over time. Additional studies identifying determining factors of discontinuation are needed to fully realize the benefits of SGLT2i.