Empagliflozin (Jardiance): Evidence‑Based Recommendations

1. Indications – Heart Failure

Empagliflozin reduces cardiovascular death and heart‑failure hospitalization in adults with heart failure across the full spectrum of ejection fractions (both HFrEF and HFpEF) 1.
The Canadian Heart Failure Society gives a strong recommendation with high‑quality evidence for empagliflozin in HFrEF patients, irrespective of type 2 diabetes status, to improve symptoms, quality of life, and to lower HF hospitalization and cardiovascular mortality 2.

Empagliflozin lowers cardiovascular mortality by 38 % relative risk in adults with type 2 diabetes and established atherosclerotic cardiovascular disease, as demonstrated in the EMPA‑REG OUTCOME trial 3.
The 2021 Canadian diabetes guidelines issue a strong recommendation with high‑quality evidence for empagliflozin in this population to reduce heart‑failure hospitalization and death 2.

The 2022 Canadian guidelines provide a strong recommendation with moderate‑quality evidence for SGLT2 inhibitors (including empagliflozin) in adults with CKD (UACR > 20 mg/mmol and eGFR ≥ 25 mL/min/1.73 m²) to lessen eGFR decline, progression to end‑stage kidney disease, kidney‑related death, all‑cause and cardiovascular mortality, non‑fatal myocardial infarction, and heart‑failure hospitalization 6.
The EMPA‑KIDNEY trial confirmed that empagliflozin improves kidney‑disease progression and reduces cardiovascular death in patients with established CKD 6.

Empagliflozin may be started when eGFR ≥ 45 mL/min/1.73 m² for any approved indication; cardiovascular and kidney benefits persist even if eGFR falls below 45 mL/min/1.73 m², provided the patient is not yet on dialysis or transplanted 5.
Glucose‑lowering efficacy diminishes at eGFR < 45 mL/min/1.73 m², but cardioprotective effects remain 5.

Empagliflozin is not recommended in type 1 diabetes because of an increased risk of DKA 2.
Patients should discontinue empagliflozin 3–4 days before scheduled surgery, during critical illness, or prolonged fasting to mitigate DKA risk 5.
Education on “sick‑day” management and clear instructions on when to stop the medication are advised 2.

Genital mycotic infections are the most common adverse effect, occurring in approximately 10–15 % of women; risk is higher in women, those with prior infections, and uncircumcised men 2.
These infections are usually managed with topical or oral antifungals without needing to discontinue empagliflozin 2.

A temporary reduction in eGFR of up to 15 % may be observed after initiating empagliflozin, typically resolving within 1–3 months 2.
Increased monitoring for acute kidney injury is recommended, especially in patients with baseline renal impairment 2.

The EMPEROR‑Reduced and EMPEROR‑Preserved trials excluded patients with eGFR < 20 mL/min/1.73 m², indicating limited evidence for empagliflozin use in severe renal dysfunction 2.
Very limited data support use in HFrEF patients with eGFR < 30 mL/min/1.73 m² 2.