Drug Update · Cardiology

FDA Approves Dapagliflozin for HFpEF: HR 0.82 for Worsening HF or CV Death

July 10, 2026

Trial

DELIVER

Randomized patients

6,263

Primary outcome event rates

16.4% (dapagliflozin) vs 19.5% (placebo)

Primary outcome HR

HR 0.82; 95% CI 0.73-0.92

Worsening HF events

11.8% vs 14.5% (HR 0.79; 95% CI 0.69-0.91)

Cardiovascular death events

7.4% vs 8.3% (HR 0.88; 95% CI 0.74-1.05)

Median follow-up

2.3 years

FDA supplemental approval date

2026-06-03

Clinical Perspective

Cardiologists and clinicians who manage adults with heart failure now have an FDA‑labeled SGLT2 inhibitor supported by DELIVER data to reduce the risk of the composite of worsening heart failure or cardiovascular death in patients with heart failure and an ejection fraction above 40% ^[2]^[1]. The DELIVER results support adding dapagliflozin to usual therapy to reduce combined worsening‑HF/CV death events versus placebo (HR 0.82; 95% CI, 0.73-0.92) ^[1]. How durable the observed benefit is beyond the DELIVER median 2.3 years of follow‑up remains a question for longer‑term observation and real‑world data ^[1].

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

The FDA has approved dapagliflozin (Farxiga) for adults with heart failure to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart‑failure visits, based on DELIVER trial results showing a benefit on the composite of worsening heart failure or cardiovascular death versus placebo (HR 0.82; 95% CI, 0.73-0.92) ^[1]^[3]. The approval is reflected in the product labeling and FDA records ^[2]^[3].

Clinical Context

Dapagliflozin is a sodium‑glucose cotransporter 2 (SGLT2) inhibitor marketed by AstraZeneca; the mechanism includes inhibition of renal SGLT2, reduced glucose reabsorption, and effects on renal sodium handling that may affect cardiac preload and afterload ^[3]. The FDA label lists indications across cardiometabolic and renal populations, including adults with heart failure, and cites cardiovascular and renal outcome data in support of those indications ^[2]^[3]. The DELIVER randomized trial tested dapagliflozin added to usual therapy in patients with heart failure and an ejection fraction >40%, reporting time‑to‑event efficacy for a composite of worsening heart failure or cardiovascular death and providing the primary outcome data used by regulators ^[1]^[2].

Key Findings

The DELIVER trial showed dapagliflozin reduced the risk of the composite of worsening heart failure or cardiovascular death versus placebo (HR 0.82; 95% CI, 0.73 to 0.92) ^[1].
In DELIVER (n=6,263 randomized), the primary outcome occurred in 512 of 3,131 patients (16.4%) in the dapagliflozin group and in 610 of 3,132 patients (19.5%) in the placebo group (median follow‑up 2.3 years) ^[1].
Worsening heart failure events occurred in 368 patients (11.8%) with dapagliflozin versus 455 patients (14.5%) with placebo (HR 0.79; 95% CI, 0.69 to 0.91) ^[1].
Cardiovascular death occurred in 231 patients (7.4%) in the dapagliflozin group and in 261 patients (8.3%) in the placebo group (HR 0.88; 95% CI, 0.74 to 1.05) ^[1].
Results were reported to be consistent across prespecified subgroups, including patients with or without diabetes and across ejection fraction strata (≥60% and <60%) ^[1].

Safety & Tolerability

The incidence of adverse events overall was reported as similar in the dapagliflozin and placebo groups in DELIVER ^[1].
The FARXIGA prescribing information lists most common adverse reactions (≥5%) as female genital mycotic infections, nasopharyngitis, and urinary tract infections ^[2].
The label includes warnings and precautions for diabetic ketoacidosis, volume depletion (including symptomatic hypotension), and serious genitourinary infections, including pyelonephritis and urosepsis ^[2].
Additional safety considerations in the label address higher incidence of hypotension‑related adverse reactions in elderly patients and volume‑depletion‑related events in patients with renal impairment ^[2].

Study Design

DELIVER was a randomized, placebo‑controlled, double‑blind trial that enrolled 6,263 patients with heart failure and a left ventricular ejection fraction >40% who were assigned to dapagliflozin 10 mg once daily or matching placebo added to usual therapy ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The primary outcome was a time‑to‑event composite of worsening heart failure (unplanned hospitalization or urgent visit for heart failure) or cardiovascular death. Median follow‑up was 2.3 years; primary analyses reported hazard ratios with 95% confidence intervals ^[1].

FAQ

Q1 What is dapagliflozin (Farxiga) approved for?

Dapagliflozin (Farxiga) is approved to reduce the risk of sustained eGFR decline, end‑stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression, and to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart‑failure visits in adults with heart failure. It is also approved for glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.

Q2 How does dapagliflozin work?

Dapagliflozin is a sodium‑glucose cotransporter 2 (SGLT2) inhibitor that reduces renal reabsorption of filtered glucose and promotes urinary glucose excretion. It also reduces sodium reabsorption in the proximal tubule, which increases distal sodium delivery and may influence intraglomerular pressure, preload and afterload, and sympathetic activity — mechanisms cited in regulatory materials as relevant to cardiovascular and renal effects.

Q3 What is the recommended dose of dapagliflozin for heart‑failure indications?

For the heart‑failure and other non‑glycemic indications in adults, the prescribing information recommends dapagliflozin 10 mg orally once daily. The DELIVER trial randomized patients to dapagliflozin 10 mg once daily versus placebo; the trial’s primary outcome and event rates supported the label update for heart‑failure indications. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects to expect?

The prescribing information lists the most common adverse reactions (incidence ≥5%) as female genital mycotic infections, nasopharyngitis, and urinary tract infections. The label also includes warnings for diabetic ketoacidosis, volume depletion and symptomatic hypotension, and serious genitourinary infections including pyelonephritis and urosepsis, and notes higher risk of hypotension‑related events in the elderly and volume‑depletion events in patients with renal impairment.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Dapagliflozin for HFpEF: HR 0.82 for Worsening HF or CV Death

FDA Approves Dapagliflozin for HFpEF: HR 0.82 for Worsening HF or CV Death

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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