SGLT2 Inhibitors for Heart Failure: Who Should Take Them?

Research-informed explainer — last updated April 12, 2026

SGLT2 inhibitors — drugs like empagliflozin (Jardiance) and dapagliflozin (Farxiga) — were developed as diabetes medications, but they turned out to be among the most effective heart failure treatments ever tested. Two large randomized trials have shown they reduce hospitalizations and cardiovascular deaths in heart failure patients whether the heart muscle is weak or preserved. In 2022, both major U.S. cardiology guidelines gave them their highest recommendation — Class I — for most heart failure patients, with or without diabetes. Yet many eligible patients still are not taking them.

This explainer draws on peer-reviewed research from heart failure specialists listed in the Convene directory. Their work includes the EMPEROR-Reduced and EMPEROR-Preserved trials, the DECLARE-TIMI 58 cardiovascular outcomes trial, the landmark 2013 ACC/AHA heart failure guideline, and epidemiological work establishing the scope of the heart failure burden in the United States.

What is heart failure?

Heart failure does not mean your heart has stopped. It means the heart is not pumping well enough to keep up with the body's demands. About 6.7 million American adults live with heart failure, and that number is expected to grow to more than 8 million by 2030 [4]. Heart failure is the leading cause of hospitalization in adults over 65 and carries a five-year mortality rate worse than many cancers.

Heart failure comes in two main types defined by ejection fraction — the percentage of blood pumped out of the heart with each beat. A normal ejection fraction is 55–70%.

Heart failure with reduced ejection fraction (HFrEF) means the heart muscle is weak, typically with an ejection fraction below 40%. This is sometimes called "systolic" heart failure.

Heart failure with preserved ejection fraction (HFpEF) means the ejection fraction is 50% or above, but the heart muscle is stiff and does not relax properly between beats. This was historically harder to treat — most drug therapies that worked in HFrEF failed to show benefit in HFpEF. Until SGLT2 inhibitors changed the picture.

What SGLT2 inhibitors are and how they work

SGLT2 stands for sodium-glucose cotransporter-2, a protein in the kidneys that reabsorbs glucose from the urine back into the blood. SGLT2 inhibitors block this protein, causing glucose to be excreted in the urine. That lowers blood sugar in people with diabetes.

But the heart benefits appear to be largely independent of blood sugar lowering. Researchers now believe SGLT2 inhibitors help the heart and kidneys through several mechanisms at once: they reduce the volume of fluid the body retains (similar to a mild diuretic), lower blood pressure, reduce inflammation and oxidative stress, and may directly improve energy use in heart muscle cells. The exact mechanism is still being studied, but the clinical results are not in doubt.

What EMPEROR-Reduced found

EMPEROR-Reduced enrolled 3,730 patients with HFrEF (ejection fraction 40% or below) and randomized them to empagliflozin 10 mg daily or placebo, on top of standard guideline-directed therapy. The primary endpoint was a composite of cardiovascular death or first hospitalization for heart failure.

The trial found that empagliflozin reduced the primary endpoint by 25% relative to placebo (hazard ratio 0.75). The absolute risk reduction meant that one patient was spared a cardiovascular death or heart failure hospitalization for every 19 treated over a median of 16 months [1]. Total hospitalizations — including repeat hospitalizations — were reduced by 30%. Kidney function declined more slowly in the empagliflozin group. The benefit appeared within weeks of starting treatment.

What EMPEROR-Preserved found

Until 2021, no drug had ever been shown to reduce hard outcomes in HFpEF. EMPEROR-Preserved changed that. The trial enrolled 5,988 patients with heart failure and ejection fraction above 40%, randomizing them to empagliflozin or placebo.

The primary endpoint — cardiovascular death or heart failure hospitalization — occurred in 13.8% of the empagliflozin group vs 17.1% of the placebo group, a 21% relative risk reduction [2]. The benefit came almost entirely from fewer heart failure hospitalizations rather than cardiovascular death reduction. But reducing hospitalization matters enormously for patients with HFpEF, who cycle in and out of the hospital with fluid accumulation. Quality of life improved in the empagliflozin group. Kidney function was better preserved.

This was the first drug therapy to convincingly reduce heart failure hospitalizations in preserved-ejection-fraction heart failure — a condition affecting roughly half of all heart failure patients and one for which there had previously been no Class I treatment.

What DECLARE-TIMI 58 found

DECLARE-TIMI 58 enrolled 17,160 patients with type 2 diabetes and either established cardiovascular disease or multiple risk factors. Patients were randomized to dapagliflozin or placebo. While the primary endpoint focused on major adverse cardiovascular events, the trial found that dapagliflozin reduced the composite of cardiovascular death or hospitalization for heart failure by 17% [3]. The heart failure hospitalization reduction was robust, at 27%.

Critically, the benefit was seen regardless of whether patients had known heart failure at baseline — suggesting the drug also prevents heart failure from developing in high-risk patients. This broader protective effect solidified the case for SGLT2 inhibitors across the cardiovascular risk spectrum.

What the guidelines now say

The 2013 ACC/AHA heart failure guideline — lead-authored by investigators whose work is represented in the Convene directory — established the evidence framework that later made room for SGLT2 inhibitors [4]. The 2022 AHA/ACC/HFSA guideline update elevated both empagliflozin and dapagliflozin to Class I recommendations (highest evidence, strongly recommended) for patients with HFrEF. For HFpEF, SGLT2 inhibitors received a Class IIa recommendation in 2022, with many cardiologists expecting this to rise to Class I as more evidence accumulates.

SGLT2 inhibitors are now considered one of four "pillars" of guideline-directed medical therapy for HFrEF, alongside beta-blockers, ACE inhibitors or ARNIs (like sacubitril/valsartan), and mineralocorticoid receptor antagonists. This four-drug combination represents the current evidence-based standard of care.

Who can take SGLT2 inhibitors?

SGLT2 inhibitors are approved for heart failure in patients with and without diabetes. The main contraindications are:

• Severely reduced kidney function (eGFR below about 20–25 mL/min/1.73m²) — the kidneys need enough function for the drug to work and be safe. Moderate kidney impairment is not a barrier.
• Type 1 diabetes — risk of a dangerous complication called diabetic ketoacidosis.
• Recurrent urinary tract infections or genital yeast infections — SGLT2 inhibitors increase glucose in the urine, which can promote these infections in susceptible patients.
• Active bladder cancer (for dapagliflozin specifically).

Most heart failure patients without these conditions can safely take SGLT2 inhibitors. The drugs are generally well-tolerated; the main side effects are genital yeast infections (more common in women) and a small increase in urinary tract infections. Neither is serious, and both are manageable.

Why are so many eligible patients still not taking them?

Real-world data consistently show that a large proportion of heart failure patients eligible for SGLT2 inhibitors are not receiving them. Several factors explain this gap.

Inertia after the diabetes label. Empagliflozin and dapagliflozin were approved for diabetes first. Many cardiologists initially viewed them as endocrinology drugs. Some patients are told the drug is "for diabetes" and decline it or have their insurance question coverage.

Concern about side effects. Early warnings about rare but serious side effects — Fournier's gangrene, leg amputations (noted with canagliflozin in one trial but not replicated for the class) — made some prescribers cautious. The absolute risk of these rare events is tiny relative to the cardiovascular benefit.

Fragmented care. Heart failure patients often see a cardiologist, a primary care doctor, and sometimes a nephrologist. None may feel clear ownership over which doctor should prescribe the SGLT2 inhibitor.

Guideline lag in practice. There is typically a multi-year delay between guideline updates and widespread adoption in clinical practice.

If you have heart failure and are not taking an SGLT2 inhibitor, it is worth asking your cardiologist whether one is appropriate for you.

Questions to ask your cardiologist

• Do I have HFrEF, HFpEF, or HFmrEF (mid-range ejection fraction), and does that affect whether an SGLT2 inhibitor is right for me?
• Is my kidney function adequate to start an SGLT2 inhibitor?
• I do not have diabetes — am I still a candidate for empagliflozin or dapagliflozin?
• Am I currently on all four pillars of guideline-directed therapy for HFrEF?
• If I am prone to urinary tract infections, how should I weigh that against the heart failure benefit?
• Will my insurance cover an SGLT2 inhibitor for heart failure if I do not have diabetes?

The bottom line

SGLT2 inhibitors represent one of the most meaningful advances in heart failure treatment in a generation. The EMPEROR-Reduced and EMPEROR-Preserved trials established that empagliflozin reduces hospitalizations and cardiovascular deaths across the ejection fraction spectrum — including in HFpEF, where almost nothing had worked before. Dapagliflozin has comparable evidence. The 2022 guidelines gave them the highest possible recommendation. These drugs are safe, generally well-tolerated, and now considered standard of care for most heart failure patients. If your heart failure treatment plan does not include an SGLT2 inhibitor, that is a conversation worth having with your cardiologist.