In a type 2 diabetic patient scheduled for CAR‑T (chimeric antigen receptor T‑cell) therapy, when should empagliflozin (Jardiance) be discontinued and what criteria determine when it can be safely restarted?

Empagliflozin Management in CAR T-Cell Therapy

Discontinue empagliflozin at least 3-4 days before CAR T-cell infusion, and do not restart until cytokine release syndrome (CRS) has completely resolved, coagulation parameters have normalized, and the patient has resumed normal oral intake—typically 7-14 days post-infusion.

Pre-Infusion Discontinuation Protocol

Timing of Discontinuation

• Stop empagliflozin 3-4 days (72-96 hours) before scheduled CAR T-cell infusion to prevent life-threatening diabetic ketoacidosis (DKA), which can occur even with normal blood glucose levels 1, 2.
• This washout period aligns with surgical perioperative guidelines, as empagliflozin should be stopped ≥3 days prior to any scheduled procedure including surgery 3.
• The extended discontinuation period is critical because CAR T-cell therapy creates multiple DKA risk factors simultaneously: acute illness/infection, reduced oral intake during hospitalization, and metabolic stress 1.

Pre-Infusion Assessment Requirements

• Verify volume status and correct any volume depletion before CAR T-cell infusion, as empagliflozin causes intravascular volume contraction and patients may still be volume depleted days after discontinuation 2.
• Obtain baseline complete blood counts with coagulation testing and comprehensive metabolic panels before proceeding with CAR T infusion 4.
• Assess renal function (eGFR and creatinine) as empagliflozin increases serum creatinine and patients with reduced renal function are at higher risk of complications 1, 2.

Alternative Glucose Management During Washout

• Establish glucose infusion if the patient remains fasting during the procedure to prevent ketoacidosis 1.
• Monitor closely for ketoacidosis with blood or urine ketone testing, not just glucose levels, as euglycemic DKA can occur with blood glucose <250 mg/dL 1, 2.
• Consider temporary insulin therapy for glycemic control during the empagliflozin washout period, particularly in patients with baseline HbA1c >8% 5.

Post-Infusion Restart Criteria

Mandatory Requirements Before Restarting

• CRS must be completely resolved before considering empagliflozin restart 4.
• Coagulation parameters must be normalized, typically requiring 7-14 days post-infusion 4.
• Patient must have resumed normal oral intake without nausea, vomiting, or reduced caloric intake 2.
• Platelet count must be >50,000/µL before restarting any medication that could affect hemostasis or volume status 4.

Additional Safety Checks

• Verify absence of active infection, particularly urinary tract or genital infections, as empagliflozin increases risk of urosepsis and pyelonephritis 2.
• Confirm adequate volume status with normal blood pressure and absence of orthostatic hypotension 1, 2.
• Reassess renal function and ensure eGFR remains ≥45 mL/min/1.73 m² (empagliflozin should not be restarted if eGFR is persistently <45 mL/min/1.73 m²) 2.
• Rule out ongoing metabolic stress including fever, ongoing inflammatory response, or need for vasopressor support 1.

High-Risk Considerations in CAR T-Cell Patients

Why This Population Is Particularly Vulnerable

• CAR T-cell therapy creates a perfect storm for DKA risk: acute illness (CRS), reduced oral intake during hospitalization, potential infection, and metabolic stress—all established risk factors for empagliflozin-associated ketoacidosis 1, 2.
• Elderly patients and those with reduced renal function (common in type 2 diabetes populations) are at even higher risk 1.
• Concomitant diuretics or low systolic blood pressure further increase volume depletion risk 1, 2.

Common Pitfalls to Avoid

• Do not restart empagliflozin prematurely simply because glucose levels are elevated—wait for all safety criteria to be met, as the cardiovascular benefits of empagliflozin do not outweigh acute DKA risk in the immediate post-CAR T period 1, 2.
• Do not rely solely on blood glucose monitoring to rule out ketoacidosis—always check ketones if DKA is suspected, as euglycemic DKA is characteristic of SGLT2 inhibitors 2.
• Do not restart if the patient is still requiring IV fluids or has poor oral intake, as reduced caloric intake is a major predisposing factor for DKA 1, 2.

Long-Term Considerations

• Once safely restarted, empagliflozin offers significant cardiovascular and renal benefits for patients with type 2 diabetes, including 38% reduction in cardiovascular mortality and 36% reduction in heart failure hospitalization 6.
• The drug is particularly valuable in this population given the cardiovascular risk associated with both diabetes and cancer survivorship 7, 6.