Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a drug class beneficial for treating type 2 diabetes, kidney disease, and cardiovascular conditions, including heart failure. Research suggests they may lower the risk of death and hospitalization in people with heart failure with or without type 2 diabetes.

People with diabetes are at risk of developing cardiovascular conditions, including heart failure.

Heart failure is a long-term condition where the heart does not effectively pump blood to the body. It often requires lifelong management that involves medications, including SGLT2 inhibitors.

Read on to learn more about SGLT2 inhibitors, how they may help decrease deaths and hospitalizations from heart failure, and when to contact a doctor.

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SGLT2 inhibitors, or gliflozins, are new medications designed to manage type 2 diabetes by controlling blood sugar (glucose) levels. They may also be beneficial for treating kidney disease and preventing heart failure.

SGLT2 inhibitors have Food and Drug Administration (FDA) approval for use along with diet and exercise to help reduce blood sugar in adults with type 2 diabetes. They do not have FDA approval to treat people with type 1 diabetes.

Some SGLT2 inhibitors have FDA approval to decrease death and hospitalizations from heart failure and cardiovascular disease.

Learn more about how SGLT2 inhibitors help people manage diabetes.

SGLT2 inhibitors are a promising new treatment option for people with and without type 2 diabetes who are at risk of death and hospitalization from heart failure.

Scientists do not yet understand the exact mechanisms by which SGLT2 inhibitors lower the risk of deaths and hospitalizations in people with heart failure. However, research into the subject has raised some theories.

A 2020 review of these theories assessed the potential mechanisms, which include:

  • Reducing interstitial fluid: The primary mechanism of SLGT2 inhibitors is to induce natriuresis, where a person’s body excretes excess sodium in their urine, and glucosuria, where they excrete excess blood sugar in their urine. This may reduce congestion of interstitial fluid, a layer of fluid that surrounds the body’s cells, reducing heart failure risk.
  • Blood pressure reduction: SLGT2 inhibitors may lower blood pressure by preventing sodium from reabsorbing into the kidneys. Lower blood pressure may reduce pressure on the heart, reducing the risk of heart failure.
  • Reducing inflammation: Inflammation is a factor in the severity of heart failure, and SLGT2 inhibitors may reduce inflammation, independent of their effects on lowering glucose levels.
  • Reducing sympathetic nervous system (SNS) activity: The SNS is a person’s in-built fight or flight response. When activated, a person’s heart rate and blood pressure increase. SLGT2 inhibitors may lower this activity, reducing a person’s blood pressure and heart rate and the pressure on the heart.
  • Increasing red blood cell production: SLGT2 inhibitors may increase erythropoiesis, the process that produces red blood cells, by increasing the release of the hormone erythropoietin from the kidney.
  • Increasing circulating ketone levels: SLGT2 inhibitors can increase levels of ketone, a chemical produced by the process through which the liver breaks down fat, also known as ketosis. The heart may use these ketones as an extra source of “fuel,” increasing cardiac efficiency, particularly in people with a failing heart.
  • Decreasing oxidative stress: SLGT2 inhibitors improve the control of blood sugar levels in a person’s body, which may decrease the production of reactive oxygen species (ROS) in the heart’s coronary cells. ROS contribute to heart failure.
  • Improving vascular function: SLGT2 inhibitors improve the function of the vascular system, also known as the circulatory system, by reducing cell dysfunction and molecular changes associated with plaque formation in the arteries.

Further to this, a 2021 study suggests SGLT2 inhibitors may reduce the risk of cardiovascular disease and decrease heart failure hospitalization due to their ability to significantly reduce intracellular sodium levels. This has a cardioprotective effect that helps prevent oxidative stress and cardiomyocyte death.

Research from 2021 suggests several SGLT2 inhibitors effectively reduce the risk of hospitalizations and deaths in people with heart failure. Its findings include the following:

  • Empagliflozin (Jardiance) may lower the risk of heart failure, hospitalization, and cardiovascular death, including from stroke and heart attack.
  • Canagliflozin (Invokana) may help lower the chance of a first major adverse cardiovascular event, kidney disease development, and heart failure hospitalization. It may also reduce the chance of stroke, heart attack, and death due to heart or blood vessel conditions.
  • Dapagliflozin (Farxiga) may help reduce the risk of a first hospitalization for heart failure.

The above study further suggests that Jardiance, Invokana, and Farxiga are useful in reducing death and hospitalizations in people with heart failure.

A 2019 study also suggests dapagliflozin may reduce the chance of heart failure worsening and cardiovascular disease deaths in people with and without type 2 diabetes.

Currently, Jardiance, Invokana, and Farxiga have FDA approval to reduce the risk of death and hospitalization in people with heart failure.

SGLT2 inhibitors do not have approval for managing symptoms or improving the function of the ventricles, the muscular chambers that pump blood out of the heart and into the circulatory system. Not all people with heart failure will benefit from them.

Other treatment options with approval to treat heart failure include ACE inhibitors and diuretics.

Over time, more SGLT2 inhibitors may gain approval.

There are several side effects associated with SGLT2 inhibitors.

A 2018 study suggests the following possible adverse side effects, noting that additional research is needed:

In 2018, the FDA also warned of a link between SGLT2 inhibitors and an extremely uncommon but life threatening bacterial infection of the genital area called necrotizing fasciitis of the perineum, also known as Fournier’s gangrene.

A person should see a healthcare professional to receive a heart failure diagnosis. This involves performing tests and reviewing an individual’s symptoms and family history of heart disease. The doctor can see if they are a suitable candidate for SGLT2 inhibitors.

The effects of SGLT2 inhibitors can vary among individuals. SGLT2 inhibitors have the potential to cause mild to serious side effects. A person should make an appointment with a doctor if they develop any unusual symptoms after taking SGLT2 inhibitors.

If heart failure symptoms worsen, a person should seek medical attention quickly.

SGLT2 inhibitors can help treat type 2 diabetes, kidney disease, and cardiovascular diseases such as heart failure.

There are several theories on how SGLT2 inhibitors lower the risk of heart failure. Studies suggest they may lower blood pressure, reduce inflammation, increase red blood cell production, and reduce fluid in the body, all of which help reduce the likelihood of complications from heart failure such as death and hospitalization.

A person should talk with their doctor to see if SGLT2 inhibitors would be a beneficial addition to their treatment plan.

SGLT2 inhibitors can interact with other drugs and cause side effects. A person should seek medical attention if they develop or have worsening symptoms.