Drug Update · Cardiology

FDA Approves Empagliflozin for Heart Failure: 21% Risk Reduction in EMPEROR-Preserved

July 10, 2026

Trial

EMPEROR-Preserved

Primary result (event rates)

415/2,997 (13.8%) empagliflozin vs 511/2,991 (17.1%) placebo

Primary result (HR)

HR 0.79; 95% CI 0.69-0.90; P<0.001

Total HF hospitalizations

407 empagliflozin vs 541 placebo (HR 0.73; 95% CI 0.61-0.88)

Trial population size

5,988 patients randomized

Recommended dose (label)

10 mg once daily in the morning

Clinical Perspective

Cardiologists, heart-failure specialists, advanced practice providers, and pharmacists managing adults with heart failure can consider empagliflozin where the intent is to reduce the risk of cardiovascular death or hospitalization for heart failure, based on the EMPEROR-Preserved trial results ^[1]^[3]. The trial-supported data show a 21% relative reduction in the composite of cardiovascular death or hospitalization for heart failure (HR 0.79; 95% CI 0.69-0.90) versus placebo, driven mainly by fewer heart-failure hospitalizations, and labeling recommends a 10 mg once-daily dose for adults with heart failure ^[1]^[3]. What remains unanswered is which patient subgroups within the broad heart-failure population derive the greatest absolute benefit and how empagliflozin should be integrated with other heart-failure therapies in specific EF ranges and clinical scenarios?

Dr. Kavya Sharma, MBBS, MD (General Medicine), DM (Cardiology) · Cardiology

The FDA approved empagliflozin (JARDIANCE) in February 2022 to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, based on the EMPEROR-Preserved trial showing a primary outcome event in 415 of 2,997 patients (13.8%) in the empagliflozin group versus 511 of 2,991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.90; P<0.001) ^[1]^[2]. The effect in EMPEROR-Preserved was driven largely by fewer hospitalizations for heart failure with empagliflozin ^[1]. Clinicians should consult current prescribing information for complete dosing guidance. ^[3]

Clinical Context

Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor marketed as JARDIANCE by Boehringer Ingelheim and partners. As an SGLT2 inhibitor, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose; it also reduces sodium reabsorption and increases delivery of sodium to the distal tubule, which may affect cardiac preload and afterload ^[4]. Regulatory labeling lists empagliflozin as indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease; labeling changes reflecting the heart-failure indication were made in 2/2022 in the prescribing highlights ^[2]^[3]. The recommended dose in adults for the heart-failure indication is 10 mg orally once daily in the morning, taken with or without food ^[3]. Clinicians should consult current prescribing information for complete dosing guidance.

Key Findings

The EMPEROR-Preserved trial showed empagliflozin reduced the risk of the composite of cardiovascular death or hospitalization for heart failure by 21% versus placebo (HR 0.79; 95% CI 0.69-0.90); the primary outcome occurred in 415 of 2,997 patients (13.8%) with empagliflozin and 511 of 2,991 patients (17.1%) with placebo ^[1].
The trial reported that the observed effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group; total hospitalizations for heart failure were 407 with empagliflozin and 541 with placebo (hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001) ^[1].
EMPEROR-Preserved enrolled patients with class II-IV heart failure and an ejection fraction of more than 40%; the effects of empagliflozin appeared consistent in patients with or without diabetes according to the trial report ^[1].

Safety & Tolerability

Genital mycotic infections and urinary tract infections were reported more frequently with empagliflozin in the trial and are listed as common adverse reactions in labeling ^[1]^[3].
Hypotension and events related to volume depletion were reported and are included in warnings and precautions in the prescribing information ^[1]^[3].
Ketoacidosis (including reports of diabetic ketoacidosis) is described in the label warnings and precautions ^[3].
Urosepsis and pyelonephritis (serious urinary tract infections) have been reported and are included in labeling ^[3].
Hypoglycemia when used with insulin or insulin secretagogues is described in the labeling ^[3].
Necrotizing fasciitis of the perineum (Fournier's gangrene) is listed in the label warnings and precautions ^[3].
Hypersensitivity reactions including angioedema have been reported and are included in the prescribing information ^[3].

Study Design

EMPEROR-Preserved was a randomized, double-blind trial that assigned 5,988 patients with class II-IV heart failure and an ejection fraction greater than 40% to receive empagliflozin 10 mg once daily or placebo, in addition to usual therapy; the primary outcome was a composite of cardiovascular death or hospitalization for heart failure ^[1]. Over a median follow-up of 26.2 months, the primary outcome occurred in 415 of 2,997 patients (13.8%) in the empagliflozin group and 511 of 2,991 patients (17.1%) in the placebo group (HR 0.79; 95% CI 0.69-0.90; P<0.001); the trial reported the effect was mainly due to fewer heart-failure hospitalizations ^[1]. Details on randomization procedures, stratification, and additional secondary endpoints are reported in the primary publication ^[1]. Clinicians should consult current prescribing information for complete dosing guidance. ^[3]

FAQ

What is empagliflozin (JARDIANCE) approved for?

Empagliflozin (JARDIANCE) is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. The labeling also indicates empagliflozin to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease, and as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. Clinicians should consult current prescribing information for complete dosing guidance.

How does empagliflozin work?

Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion. The prescribing information also notes that empagliflozin reduces sodium reabsorption and increases delivery of sodium to the distal tubule, which may influence physiologic functions relevant to heart failure such as lowering pre- and afterload.

What is the recommended dose of empagliflozin for heart failure?

The recommended dose of JARDIANCE for adults is 10 mg orally once daily in the morning, taken with or without food; for glycemic control the dose may be increased to 25 mg in patients tolerating 10 mg once daily per labeling, but the heart-failure indication is supported at 10 mg once daily in the trial and in labeling. Clinicians should consult current prescribing information for complete dosing guidance.

What are the most common side effects of empagliflozin?

The most common adverse reactions reported with empagliflozin include urinary tract infections and female genital mycotic infections, and the EMPEROR-Preserved trial and labeling report higher rates of genital and urinary tract infections and hypotension or events related to volume depletion with empagliflozin. Labeling also describes warnings and precautions for ketoacidosis, urosepsis and pyelonephritis, hypoglycemia when used with insulin or insulin secretagogues, necrotizing fasciitis of the perineum (Fournier's gangrene), and hypersensitivity reactions including angioedema. Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Empagliflozin for Heart Failure: 21% Risk Reduction in EMPEROR-Preserved

FDA Approves Empagliflozin for Heart Failure: 21% Risk Reduction in EMPEROR-Preserved

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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