Off-Label Uses of Jardiance (Empagliflozin)
Jardiance is most commonly used off-label for heart failure without diabetes, particularly heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) in patients who do not have type 2 diabetes.
Primary Off-Label Indication: Heart Failure Without Diabetes
Heart Failure with Reduced Ejection Fraction (HFrEF)
- Empagliflozin significantly reduces cardiovascular death and heart failure hospitalization in patients with HFrEF regardless of diabetes status 1.
- In the EMPEROR-Reduced trial, empagliflozin 10 mg daily reduced the primary composite outcome of cardiovascular death or hospitalization for worsening heart failure by 21% (HR 0.79 [95% CI 0.69–0.90]) in patients with NYHA class II-IV heart failure and ejection fraction ≤40% 1.
- Approximately 50% of subjects in EMPEROR-Reduced had type 2 diabetes at baseline, meaning the other 50% did not have diabetes—demonstrating efficacy in non-diabetic heart failure 1.
- The effects of empagliflozin were consistent in people with or without diabetes, establishing this as a robust off-label use 1.
Heart Failure with Preserved Ejection Fraction (HFpEF)
- EMPEROR-Preserved demonstrated that empagliflozin reduces cardiovascular death or hospitalization for heart failure in HFpEF patients (LVEF >40%) by 21% (HR 0.79 [95% CI 0.69–0.90]) 1.
- This trial included 5,988 adults with NYHA functional class I-IV chronic HFpEF, with approximately 50% having type 2 diabetes at baseline 1.
- The benefit was consistent regardless of diabetes diagnosis, making this a well-established off-label indication 1.
Supporting Evidence Across Heart Failure Spectrum
- A large meta-analysis including EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and SOLOIST-WHF (21,947 patients total) demonstrated reduced risk for cardiovascular death or hospitalization for heart failure, cardiovascular death, first hospitalization for heart failure, and all-cause mortality 1.
- These findings indicate that SGLT2 inhibitors reduce the risk for heart failure hospitalization and cardiovascular death in a wide range of people with heart failure, with or without diabetes 1.
Secondary Off-Label Uses
Type 1 Diabetes
- Empagliflozin has been used off-label in type 1 diabetes following strict protocols to improve glycemic control 2.
- In a prospective study of 27 patients with type 1 diabetes, empagliflozin added to insulin therapy significantly reduced HbA1c from 8.0% ± 0.7% to 7.2% ± 0.8% (P < 0.001) at 52 weeks 2.
- Time in range for capillary glucose monitoring increased from 50% to 62% (P = 0.008) with a reduction in insulin requirements of -0.08 IU/(kg·day) 2.
- Body weight decreased by 8 kg and systolic blood pressure decreased from 134 to 127 mmHg 2.
Critical Safety Caveat: The FDA label explicitly states that Jardiance is not for people with type 1 diabetes as it may increase their risk of diabetic ketoacidosis 3. One patient in the study developed mild diabetic ketoacidosis requiring empagliflozin withdrawal 2. This off-label use requires strict protocols, patient education, and close monitoring for ketoacidosis 2.
Investigational: Brain Tumors (Astrocytomas)
- Preliminary research suggests empagliflozin may inhibit glucose uptake in astrocytomas 4.
- In a small study of 5 patients (4 with WHO grade IV glioblastomas, 1 with grade II astrocytoma), a single oral dose of Jardiance (25 or 100 mg) reduced tumor glucose accumulation measured by PET imaging 4.
- SGLT2 is expressed in human brain tumors, and this represents a potential future off-label use pending clinical trials 4.
Dosing for Off-Label Heart Failure Use
- The recommended dose is 10 mg orally once daily, which is the lowest dose tested in cardiovascular and heart failure outcomes trials 1.
- No further dose titration is needed for cardiovascular or heart failure risk reduction 1.
- Dose modifications are required based on renal function: use is not recommended for glycemic control if eGFR <45 mL/min/1.73 m², and contraindicated if on dialysis or with severe renal impairment 1.
Important Safety Considerations for Off-Label Use
Ketoacidosis Risk
- SGLT2 inhibitors increase susceptibility to diabetic ketoacidosis, including euglycemic ketoacidosis, particularly with insulin pump malfunctions, significant insulin dose reductions, or prolonged fasting 1.
- Patients should be educated to check for ketones if experiencing nausea, vomiting, abdominal pain, or tiredness, even if blood sugar is <250 mg/dL 3.
Volume Depletion
- Empagliflozin causes osmotic diuresis leading to intravascular volume contraction 3.
- Consider stopping or reducing diuretic dose when initiating therapy, especially in patients at higher risk (age ≥65 years, low sodium diet, kidney problems, or taking diuretics) 1, 3.
Genitourinary Infections
- Increased risk of genital mycotic infections and urinary tract infections 1, 3.
- In the type 1 diabetes study, genitourinary infections occurred in 10 episodes over 52 weeks 2.