Jardiance vs. Entresto for Heart Failure

Heart failure is a condition that happens when the heart doesn’t effectively pump blood to the body. It affects over 6 million adults in the U.S. and can be difficult to treat. Usually, people with heart failure have to take several medications to stop their condition from getting worse.

The two most common types of heart failure are heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Many medications are used to treat HFrEF, including angiotensin-converting enzyme (ACE) inhibitors and beta blockers. However, HFpEF historically has not had as many FDA-approved treatments available — until recently.

In the past two years, the FDA approved Jardiance (empagliflozin) and Entresto (sacubitril/valsartan) to treat heart failure more broadly, focusing on HFpEF. Here, we’ll review these two medications and how they help treat HFpEF. 

What is Jardiance?

Jardiance belongs to a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. Jardiance mainly works in the kidney by stopping you from absorbing sugar, causing you to urinate it out instead. 

What conditions is Jardiance approved to treat?

Jardiance was originally approved to treat Type 2 diabetes. However, research found that it could also be used for other health problems, like protecting the kidneys or the heart.

Currently, Jardiance is FDA-approved to:

• Treat Type 2 diabetes along with a healthy diet and exercise

• Lower the risk of heart-related death in people with Type 2 diabetes and heart disease

• Lower the risk of death and hospital stays due to HFrEF or HFpEF

How does Jardiance work for HFpEF?

It’s believed Jardiance may work for HFpEF in several ways:

• By removing fluid and sodium from the body

• By stopping the heart from changing shape over time

• By lowering the amount of heart inflammation (swelling)

• By lowering blood pressure

• By helping the heart to pump more effectively

Experts continue to study Jardiance to find out if it helps treat heart failure in any other ways.

What is Entresto?

Entresto is a combination of two medications: sacubitril and valsartan. Sacubitril is an angiotensin receptor neprilysin inhibitor (ARNI). It’s currently the only FDA-approved ARNI and is only found in Entresto. Valsartan is an angiotensin II receptor blocker (ARB). Valsartan is available by itself, marketed under the brand name Diovan and as a generic.

What conditions is Entresto approved to treat?

Entresto is FDA-approved to treat heart failure in both adults and children. For adults with heart failure, it can be prescribed for either HFrEF or HFpEF. But it’s most beneficial for people with an ejection fraction (EF) that’s below normal or on the lower side of normal.

An EF is a measurement that represents how much blood your heart is pumping out to your body. An EF between 50% and 70% is considered normal. People with HFrEF have an EF under 40%. People with HFpEF have an EF that’s at least 40%, but they may have a normal EF.

How does Entresto work for HFpEF?

The medications in Entresto work together to help the heart pump better. They relax the blood vessels and help prevent fluid from building up, which causes many heart failure complications.

Entresto also helps stop the body from making certain chemicals that are thought to cause the heart to change shape over time. These shape changes make the heart muscle stiff and pump less efficiently.

How are Jardiance and Entresto dosed and given?

Jardiance and Entresto are both tablets that you take by mouth. But, they’re a little different in how they are taken.

Jardiance is taken once a day in the morning with or without food. It comes available as 10 mg and 25 mg tablets, but you only need to take 10 mg for heart failure. The higher strength is only recommended when treating diabetes.

Entresto comes in three different strengths. Most people start with the 49 mg/51 mg strength twice daily. Your healthcare provider may raise your dose a few weeks later, depending on how you respond. If you’ve been taking an ACE inhibitor, like lisinopril, you’ll need to stop taking it for a few days before starting Entresto.

How effective are Jardiance and Entresto for treating HFpEF?

Both Entresto and Jardiance are FDA-approved for HFrEF and HFpEF. But, there are questions about which is better for HFpEF. It’s important to note that Entresto and Jardiance haven’t been directly compared to each other in clinical trials yet.

In studies, Jardiance lowered the number of HFpEF-related hospitalizations and deaths. A similar benefit was seen for all study participants taking Jardiance, regardless of their EF. This clinical trial compared Jardiance to placebo (a pill with no medication in it).

In a different clinical trial, Entresto was compared to valsartan (one of the two ingredients in Entresto). Entresto helped lower the number of HFpEF hospitalizations and deaths compared to valsartan. But, these results weren’t statistically significant for all study participants.

Entresto helped some people with HFpEF more than others. Entresto had the best effects for people with an EF between 45% and 57% and for women. So not all people with HFpEF may benefit from Entresto.

Recently, experts released new guidelines for treating HFpEF. Currently, both Entresto and Jardiance can be used to treat the condition. However, recent studies suggest that medications like Jardiance may have more evidence to support their use over Entresto. But Jardiance may not be right for everyone. Your healthcare provider can help you understand why they chose one over the other for you.

What are the known side effects of Jardiance and Entresto?

Since Jardiance and Entresto are from different classes of medications, they have different side effects.

Jardiance’s common side effects include urinary tract infections (UTIs) and yeast infections. Less commonly, it can cause low blood sugar, dehydration, and kidney damage. Jardiance isn’t recommended for people with severe kidney problems or those on dialysis.

Entresto’s common side effects include:

• Low blood pressure

• High potassium levels

• Cough

• Dizziness

• Kidney problems

Entresto can also cause swelling of the face, lips, and neck. This is called angioedema, and it can be life-threatening. If you’ve experienced angioedema with ACE inhibitors or ARBs before, you shouldn’t take Entresto. This medication should also be avoided if you’re pregnant, as it’s known to harm unborn babies.

What interactions do Jardiance and Entresto have?

Jardiance can interact with other diabetes medications, raising your risk of severely low blood sugar. It also interacts with diuretics (water pills), making dehydration more likely. It’s important to know that Jardiance can be combined with these other medications if needed. But caution should be taken to help prevent problems.

Entresto interacts with the following:

• ACE inhibitors, such as enalapril (Vasotec)

• ARBs, such as losartan (Cozaar)

• Lithium

• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin)

• Potassium-sparing diuretics, such as spironolactone (Aldactone)

These may not be the only interactions for Jardiance and Entresto. It’s important to share an updated medication list with your pharmacist and healthcare provider. They’ll review this list and make sure it’s safe for you to take them.

How to save on Jardiance and Entresto

Jardiance and Entresto are only available as brand-name medications. But GoodRx can help you navigate ways to save on your prescription.

• Save with patient assistance programs. If you’re uninsured or underinsured, you may be eligible for the Jardiance or Entresto patient assistance programs, which offer the medications at no charge.

• Save with a copay savings card. If you have commercial insurance and meet eligibility requirements, Jardiance’s price is as little as $10 if you use the manufacturer’s savings card. Entresto’s price is also as little as $10 if you use the manufacturer’s savings card.

Can you take Jardiance and Entresto together?

Yes, you can take Jardiance and Entresto together. Current guidelines recommend combining them to treat HFrEF in some cases. In the HFpEF studies discussed earlier, some people were taking both. Whether you should be on both varies and is a decision best made with your healthcare provider.

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Written by:

Timothy Aungst, PharmD

Timothy Aungst, PharmD, has worked in pharmacy practice for the past decade with different roles and responsibilities. He has served as an associate professor of pharmacy practice for almost a decade, a clinical pharmacist in outpatient cardiology management, and now in home healthcare.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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