Dapagliflozin in Dialysis Patients
Do Not Initiate Dapagliflozin in Patients Already on Dialysis
Dapagliflozin should not be started in patients on chronic maintenance dialysis (hemodialysis or peritoneal dialysis) because there is insufficient evidence of efficacy or safety in this population, and the drug's mechanism of action—inhibition of renal sodium-glucose cotransporter-2—is rendered ineffective when native kidney function is absent. 1
- The KDOQI Work Group explicitly recommends against using dapagliflozin in patients on dialysis due to lack of proven efficacy and safety data 1
- Efficacy and safety trials with dapagliflozin (DAPA-CKD, DAPA-HF, DELIVER) did not enroll patients on dialysis, leaving no randomized controlled trial evidence to support its use in this setting 2, 3
- The glucose-lowering mechanism of SGLT2 inhibitors requires functioning nephrons to block tubular glucose reabsorption; in dialysis patients, this pathway is absent 1
Continuation in Patients Who Progress to Dialysis While Already Taking Dapagliflozin
If a patient was already taking dapagliflozin before dialysis began, the drug may be continued until dialysis is initiated, but should be discontinued once regular dialysis treatments start. 2
- The FDA label states that once enrolled in the DAPA-CKD and DELIVER trials, patients were not required to discontinue therapy if dialysis was initiated, but this reflects trial protocol continuation rather than a recommendation for routine clinical practice 2
- The KDOQI guidelines note that ongoing trials are exploring potential benefits of SGLT2 inhibitors in dialysis patients, but until these trials are completed, dapagliflozin should not be used in this population 1
Pharmacokinetic Evidence in Dialysis
- A 2023 pharmacokinetic study found that dapagliflozin was well tolerated in dialysis patients, with only 0.10% of the administered dose recovered from dialysate, indicating minimal dialyzability 4
- The drug showed nonaccumulating pharmacokinetic properties with a peak concentration (C max) of 117 ng/ml in kidney failure patients versus 97.6 ng/ml in controls, and an accumulation ratio of 26.7% versus 9.5% 4
- Despite acceptable pharmacokinetics, this single-center study does not provide efficacy data or justify clinical use in dialysis patients 4
Rationale for Discontinuation
- Loss of therapeutic target: The cardiovascular and renal protective benefits of dapagliflozin demonstrated in DAPA-CKD (39% reduction in kidney disease progression, 29% reduction in cardiovascular death or heart failure hospitalization) were observed in patients with eGFR 25–75 mL/min/1.73 m² who retained native kidney function 3, 5
- Absence of outcome data: No randomized trial has demonstrated that continuing dapagliflozin after dialysis initiation reduces mortality, cardiovascular events, or improves quality of life 1
- Potential risks without proven benefit: Genital mycotic infections and urinary tract infections remain potential adverse effects even in dialysis patients, but without demonstrated efficacy, the risk-benefit ratio is unfavorable 1
Clinical Decision Algorithm
- For patients not yet on dialysis with eGFR ≥20 mL/min/1.73 m²: Initiate or continue dapagliflozin 10 mg daily for cardiovascular and renal protection 6, 3
- For patients with progressive CKD approaching dialysis (eGFR 20–25 mL/min/1.73 m²): Continue dapagliflozin until dialysis is initiated 2, 7
- At the time of dialysis initiation: Discontinue dapagliflozin 1
- For patients already on dialysis: Do not start dapagliflozin 1
Common Pitfall to Avoid
- Do not continue dapagliflozin indefinitely in dialysis patients based solely on the FDA label's statement that trial participants were not required to discontinue at dialysis initiation—this reflects trial protocol flexibility rather than evidence of benefit, and current guidelines recommend discontinuation 1, 2