Sodium glucose cotransporter 2 (SGLT2) inhibitors are a newer, second line of medical treatment for the management of blood sugar levels in people with type 2 diabetes.

SGLT2 inhibitors may help a person better manage their blood sugar levels and lose weight when their current treatment is not effective.

This article will cover how SGLT2 inhibitors work, who can use them, and their benefits.

The kidneys play an important role in maintaining stable blood sugar levels by filtering excess glucose in the bloodstream. SGLT2 inhibitors work by blocking the reabsorption of glucose from the kidneys back into the bloodstream.

Instead, explained Dr. Sarah Rettinger — an endocrinologist at Providence Saint John’s Health Center in Santa Monica, CA — excess glucose is expelled from the body through the urine. She said that this makes SGLT2 inhibitors “very useful” in helping some people lower their blood sugar levels.

SGLT2 inhibitors are usually not the first line of treatment for people with type 2 diabetes. Dr. Rettinger often prescribes SGLT2 inhibitors to people with type 2 diabetes who are not reaching their HbA1c goals with their current medication regimen.

Recent research suggests that SGLT2 inhibitors may be appropriate for people with type 2 diabetes who are not interested in using insulin to lower their blood sugar.

Dr. Rettinger also considers SGLT2 inhibitors for people with certain comorbid conditions, including:

  • cardiovascular disease
  • heart failure
  • kidney disease

The Food and Drug Administration (FDA) have approved the following SGLT2 inhibitors to treat type 2 diabetes:

  • canagliflozin (Invokana)
  • dapagliflozin (Farxiga)
  • empagliflozin (Jardiance)
  • ertugliflozin (Steglatro)

Several combination drugs are also FDA-approved for use in people with type 2 diabetes. These include:

  • canagliflozin/metformin (Invokamet, Invokamet XR)
  • dapagliflozin/metformin (Xigduo XR)
  • dapagliflozin/saxagliptin (Qtern)
  • empagliflozin/linagliptin (Glyxambi)
  • empagliflozin/metformin (Synjardy, Synjardy XR)
  • ertugliflozin/metformin (Segluromet)
  • ertugliflozin/sitagliptin (Steglujan)

The different medications vary in their dosage levels as well as how and when a person should take them. People often take SGLT2 inhibitors with other diabetes medications, such as metformin.

A person should talk with a doctor about whether any of these medications would be appropriate and effective for them.

SGLT2 inhibitors may help reduce blood sugar levels in people with type 2 diabetes who do not see their numbers changing while taking other medications, explained Dr. Rettinger.

The drug may also offer other potential benefits, especially for the heart and kidneys.

Some research suggests that SGLT2 inhibitors may help protect the heart. For people with heart failure, “some agents in this class reduce the risk of death,” said Dr. Rettinger. This is true even in people who do not have type 2 diabetes.

The medication may also lower the risk of worsening kidney function in people with chronic kidney disease, Dr. Rettinger added.

One 2019 review of studies suggests that SGLT2 inhibitors reduce the risk of dialysis, transplantation, or death due to kidney disease in people with type 2 diabetes.

A 2018 study of SGLT2 inhibitors notes the following potential benefits:

  • a reduction of HbA1c levels
  • increased high-density lipoprotein, or “good,” cholesterol levels
  • decreased intestinal absorption of low-density lipoprotein (LDL), or “bad,” cholesterol, along with an increase in LDL passed in stool
  • a decrease in hypertension
  • sustained weight loss
  • a reduction in albuminuria, which is a sign of kidney disease that occurs when too much albumin is present in the urine

SGLT2 inhibitors may pose several risks. Dr. Rettinger noted that increased glucose in the urine makes people more susceptible to developing urinary tract infections or yeast infections.

In 2018, the FDA warned that SGLT2 inhibitors are linked to an extremely rare but life threatening bacterial infection of tissues in the pelvic floor called necrotizing fasciitis of the perineum (also known as Fournier’s gangrene).

A 2018 study suggests that although additional research is needed, SGLT2 inhibitors may increase the risk of:

  • genital and urinary tract infections
  • diabetic ketoacidosis
  • cancer
  • bone fracture
  • foot and leg amputation

Dr. Rettinger said that she does not prescribe SGLT2 inhibitors to people who have a history of:

  • frequent urinary tract infections or yeast infections
  • very low bone density or frequent falls
  • diabetes-related foot ulcers

She also does not recommend these drugs to people who:

  • are bed-bound
  • have very low blood pressure
  • may be prone to diabetic ketoacidosis, including those who have pancreatitis or a history of drug or alcohol misuse

SGLT2 inhibitors are a newer medication used to reduce blood sugar levels in people with type 2 diabetes. The medications may also reduce the risk of heart disease and kidney disease and may help some people lose weight.

However, SGLT2 inhibitors are not for everyone. Side effects may include decreased blood pressure and an increased risk of urinary tract or yeast infections.