Investigators examined whether dapagliflozin is safe to use in patients on dialysis in a small pilot study.
In DARE-ESKD (ClinicalTrials.gov identifier: NCT05343078), Andrei C. Sposito, MD, PhD, of Cidade Universitária in São Paulo, Brazil, and colleagues investigated the dialyzability and pharmacokinetics of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) in 5 patients receiving hemodialysis and 2 patients performing peritoneal dialysis. All patients had an estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73m2, including 3 patients with residual kidney function of 300 mL per day. Patients with liver conditions were excluded.
Dapagliflozin 10 mg was administered to patients almost daily for 7 days. The peak dapagliflozin concentration was 117 ng/mL in the dialysis group compared with 97.6 ng/mL in a control group who had diabetes and an eGFR of 60 mL/min/1.73m2 or more, Dr Sposito’s team reported in the Clinical Journal of the American Society of Nephrology. Drug accumulation ratios were 26.7% and 9.5% in the groups, respectively. The investigators recovered just 0.10% of the administered predialysis dapagliflozin dose in dialysate.
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No serious adverse events were reported. One patient experienced nausea.
According to Dr Sposito’s team, “these results set the ground for future investigations aimed at evaluating the persistence of the SGLT2i cardiovascular benefits in patients with kidney failure, including those on dialysis, as it was demonstrated in patients with less advanced CKD.”
The study is limited by its small sample size and the myriad differences between patients.
In an accompanying editorial, Wendy St Peter, PharmD, of the University of Minnesota in Minneapolis and Calvin Meaney, PharmD, BCPS, of the University at Buffalo School of Pharmacy and Pharmaceutical Sciences in Buffalo, New York, commented on the ongoing efforts to reduce cardiovascular risk in this population.
“Cardiovascular disease is an enigma in kidney failure. It is the leading cause of mortality, yet no known treatments prevent it, even those that are effective in the nonkidney failure populations. If SGLT2is are to break this mold, clinical trials with dosing informed by robust pharmacokinetic studies are necessary. The ongoing DAPA HD trial (NCT05179668) is evaluating dapagliflozin 10 mg daily on change in left ventricular mass over 6 months.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
References
Barreto J, Borges C, Betoni Rodrigues T, et al. Pharmacokinetic properties of dapagliflozin in hemodialysis and peritoneal dialysis patients. Clin J Am Soc Nephrol. 18(8):1051-1058. Published online August 1, 2023. doi:10.2215/CJN.0000000000000196
St Peter WL, Meaney CJ. Extending SGLT2 inhibitor use for people undergoing dialysis? Clin J Am Soc Nephrol. Published online August 1, 2023. 18(8):991-993. doi:10.2215/CJN.0000000000000232
