Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

Reviewed by: HU Medical Review Board | Last updated: August 2023

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of drugs approved to treat certain types of heart failure (HF). SGLT2 inhibitors were first used to treat type 2 diabetes. Clinical trials have shown that they also improve health outcomes for people with HF.1,2

There are currently 2 SGLT2 inhibitors approved by the US Food and Drug Administration (FDA) for HF. SGLT2 inhibitors cause few side effects. Talk to your doctor about the benefits and risks of SGLT2 inhibitors.2,3

How do SGLT2 inhibitors work?

Our kidneys help filter glucose (a type of sugar) and absorb it back into the body. A protein called SGLT2 performs this function. Blocking SGLT2 reduces how much glucose is absorbed into your body. This lowers your blood sugar by increasing how much glucose is excreted in urine. This is why SGLT2 inhibitors have been used to treat type 2 diabetes.1,2

We do not yet know how SGLT2 inhibitors work to treat HF. Their benefits for the heart seem unrelated to their effects on blood sugar. SGLT2 inhibitors may work in different ways to treat HF by:2,4

  • Reducing inflammation
  • Restoring kidney function
  • Lowering heart rate and blood pressure
  • Reducing heart muscle wall tension
  • Reducing the heart’s workload
  • Increasing red blood cell production

Guidelines recommend SGLT2 inhibitors for people with “reduced ejection fraction.” This is when the heart muscle does not contract well. The heart pumps less oxygen-rich blood into the body.1

Examples

Two SGLT2 inhibitors are currently FDA-approved to treat people with HF. These are:3

  • Jardiance® (empagliflozin)
  • Farxiga® (dapagliflozin)

Clinical trials have shown that Jardiance and Farxiga:5,6

  • Reduce the risk of major cardiovascular events
  • Reduce the risk of death from HF
  • Reduce hospitalizations for HF

SGLT2 inhibitors take less than a month to start showing benefits. This is why experts recommend starting them quickly in people hospitalized with HF.1

What are the possible side effects?

Side effects vary depending on the specific drug you are taking. Some common side effects of SGLT2 inhibitors include:5,6

  • Urinary tract infections
  • Vaginal yeast infections
  • Stuffy or runny nose
  • Sore throat
  • Changes in urination

SGLT2 inhibitors can cause life-threatening ketoacidosis. This is an increased level of ketones in your blood or urine. It can happen in people with diabetes. Talk to your doctor if you notice symptoms of ketoacidosis, such as:5,6

  • Nausea
  • Vomiting
  • Stomach pain
  • Tiredness
  • Trouble breathing

SGLT2 inhibitors can cause dehydration. Talk to your doctor if you notice signs of dehydration, including:5,6

  • Dizziness
  • Fainting
  • Light-headedness

Other side effects are rare, but possible. These include:5,6

  • Serious urinary tract infections
  • Low blood sugar (hypoglycemia) when taking another drug that lowers blood sugar
  • Fournier’s gangrene (bacterial infection around the anus and genitals)
  • Yeast infection of the penis
  • Allergic reactions

These are not all the possible side effects of SGLT2 inhibitors. Talk to your doctor about what to expect when taking SGLT2 inhibitors. You also should call your doctor if you have any changes that concern you when taking SGLT2 inhibitors.

Other things to know

Take SGLT2 inhibitors exactly as your doctor prescribes. They are usually taken once a day by mouth. Certain types must be taken in the morning before having food. Other types can be taken any time of day with or without food.5,6

Certain other medicines and health conditions make SGLT2 inhibitors unsafe. Before beginning treatment for HF, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

In addition, be sure to tell your doctor about:5,6

  • Any kidney, liver, or pancreas problems
  • Any history of urinary tract infections
  • Changes in your diet
  • Amount of alcohol you drink
  • Whether you take diuretics (water pills) or medicines that lower blood sugar
  • Pregnancy or plans to become pregnant
  • Breastfeeding or plans to breastfeed

For more information, read the full prescribing information of Farxiga and Jardiance.

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