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Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

Reviewed by: HU Medical Review Board | Last reviewed: February 2024

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

There are currently 3 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 filter a significant amount of glucose (a type of sugar) into the urine. Under normal circumstances, close to 100 percent of this glucose is absorbed back into the body. A protein called SGLT2 performs this function.1,2

Blocking SGLT2 reduces how much glucose is absorbed back into your body. This lowers your blood sugar by increasing how much glucose your body sends out in your 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 heart failure. Their benefits for the heart seem unrelated to their effects on blood sugar. SGLT2 inhibitors may work in different ways to treat heart failure by:2,4

  • Reducing inflammation
  • Restoring kidney function
  • Lowering heart rate and blood pressure
  • Reducing tension in the walls of the heart muscle
  • Expelling excess fluid and sodium in urine
  • Reducing the heart’s workload
  • Increasing red blood cell production

Current guidelines strongly recommend SGLT2 inhibitors for people with “reduced ejection fraction.” This is when the heart muscle does not contract well. This causes the heart to pump less oxygen-rich blood into the body.1

Examples

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

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

Clinical trials have shown that these SGLT2 inhibitors reduce:5-7

  • Risk of major cardiovascular events
  • Risk of death from heart failure
  • Hospitalizations for heart failure

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 can vary depending on the specific drug you are taking. Some common side effects of SGLT2 inhibitors include:5-7

  • Infections of the urinary tract and vagina
  • Stuffy or runny nose
  • Sore throat
  • Changes in urination
  • Dehydration (not enough fluid in your body)
  • Diarrhea
  • Low blood sugar

SGLT2 inhibitors can cause life-threatening ketoacidosis. This is indicated by an increased level of ketones in your blood or urine. It can happen in people with diabetes. In contrast to most cases of diabetic ketoacidosis, where blood sugar is typically high, in ketoacidosis while taking an SGLT2 inhibitor, blood sugar may or may not be high. Talk to your doctor if you notice symptoms of ketoacidosis, such as:5-8

  • Excessive thirst
  • Weakness or fatigue
  • Nausea
  • Vomiting
  • Stomach pain
  • Excessive or constant tiredness
  • Trouble breathing

SGLT2 inhibitors can cause serious dehydration. Talk to your doctor if you notice signs of dehydration, including:5-7

  • Dizziness
  • Fainting
  • Light-headedness

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

Before starting treatment with any SGLT2 drug, be sure to tell your doctor if you:5-7

  • Have any allergies
  • Have upcoming surgeries, as some SGLT2 inhibitors may need to be stopped several days before certain procedures
  • Have any kidney, liver, or pancreas problems, including history of type 1 diabetes, diabetic ketoacidosis, or urinary tract infections
  • Have changes in your diet
  • Drink alcohol
  • Take diuretics (water pills) or medicines that lower blood sugar
  • Are pregnant, planning to be pregnant, or breastfeeding

Certain other medicines and health conditions make SGLT2 inhibitors unsafe. Before beginning treatment for heart failure, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.5-7

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

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