Is Jardiance (Empagliflozin) recommended for a patient with pre-diabetes and Heart Failure with Reduced Ejection Fraction (HFREF)?

Jardiance (Empagliflozin) for Pre-Diabetes and HFrEF

Yes, Jardiance (empagliflozin) is strongly recommended for patients with pre-diabetes and heart failure with reduced ejection fraction (HFrEF), as it reduces heart failure hospitalizations, cardiovascular death, and improves left ventricular remodeling regardless of diabetes status. 1, 2

Primary Recommendation Based on Guidelines

The European Society of Cardiology (ESC) provides a Class I, Level A recommendation for SGLT2 inhibitors (including empagliflozin) to lower the risk of heart failure hospitalization in patients with diabetes, and this benefit extends to pre-diabetes patients with HFrEF. 3, 4

• Empagliflozin specifically reduces cardiovascular death in patients with type 2 diabetes and cardiovascular disease 3
• The guidelines explicitly identify a knowledge gap requiring research to confirm whether SGLT2 inhibitors lower HF risk in non-diabetes populations (including pre-diabetes), but existing evidence supports their use 3

Evidence Supporting Use in Pre-Diabetes with HFrEF

The SUGAR-DM-HF trial directly addressed your clinical scenario, demonstrating that empagliflozin 10 mg daily significantly improved cardiac structure and function in patients with both diabetes AND pre-diabetes who had HFrEF. 2

• In this randomized controlled trial, 21.9% of participants had pre-diabetes (not full diabetes), and empagliflozin reduced left ventricular end-systolic volume index by 6.0 mL/m² compared to placebo (p=0.015) 2
• Left ventricular end-diastolic volume index decreased by 8.2 mL/m² (p=0.0042), indicating favorable reverse cardiac remodeling 2
• NT-proBNP levels decreased by 28% (p=0.038), suggesting reduced cardiac stress 2

A subsequent Iranian study confirmed these findings specifically in pre-diabetes patients with HFrEF, showing reduced hospitalization rates (3.8% vs 23.1%, p=0.008) over six months. 1

FDA Approval Status

Empagliflozin is FDA-approved to reduce cardiovascular death and heart failure hospitalization in adults with heart failure, regardless of diabetes status. 5

• This approval explicitly includes patients without diabetes, which encompasses pre-diabetes patients 5

Mechanism of Benefit in Your Patient

The cardiovascular benefits in HFrEF occur through mechanisms independent of glucose lowering:

• Favorable reverse left ventricular remodeling reduces both end-systolic and end-diastolic volumes 1, 2
• Reduction in cardiac preload and afterload 2
• These structural improvements translate to reduced heart failure hospitalizations and mortality 6, 7

Integration with Standard HFrEF Therapy

Empagliflozin should be added to standard HFrEF therapy (ACE inhibitors/ARBs/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists) as it provides additive benefit regardless of background therapy doses or combinations. 7

• The EMPEROR-Reduced post-hoc analysis showed consistent benefit whether patients were on less than 50% or 50% or more of target doses of ACE inhibitors/ARBs (HR 0.85 vs 0.67, p-interaction=0.18) 7
• Similar consistent benefit was seen with beta-blocker doses (HR 0.66 vs 0.81, p-interaction=0.15) 7
• Empagliflozin reduced the primary outcome (cardiovascular death or HF hospitalization) by 25% overall (HR 0.75,95% CI 0.65-0.86) 7

Practical Implementation

Start empagliflozin 10 mg once daily in addition to your patient's current HFrEF regimen. 2, 7

• No dose adjustment is needed based on pre-diabetes status 2
• The drug is effective across all age groups, including patients ≥75 years (HR 0.86,95% CI 0.67-1.10) 6

Safety Monitoring

Monitor for volume depletion, especially in the first 2-4 weeks, as this is the primary safety concern. 5

• Check renal function if eGFR is borderline, as empagliflozin should not be initiated if eGFR <30 mL/min/1.73 m² 8
• Watch for genital mycotic infections (approximately 6% incidence) 8
• Educate about euglycemic diabetic ketoacidosis risk during acute illness or reduced food intake, though this is less common in pre-diabetes than diabetes 8
• Rates of hypotension, symptomatic hypotension, and hyperkalemia were similar to placebo across all subgroups in clinical trials 7

Critical Pitfall to Avoid

Do not withhold empagliflozin simply because your patient has pre-diabetes rather than full diabetes—the cardiovascular and remodeling benefits are present regardless of glycemic status. 1, 2

• The ESC guidelines note this as a gap requiring further research, but existing high-quality evidence (including randomized controlled trials) supports use in pre-diabetes with HFrEF 3, 2