SGLT2 Inhibitors (Type 2 Diabetes Drug Class)

SGLT2 (sodium-glucose co-transporter 2) inhibitors are prescription oral medications used to treat type 2 diabetes.

• SGLT2 inhibitors are used alone or in combination with metformin or other diabetic medications and with exercise and diet to reduce blood glucose in adults with type 2 diabetes.
• SGLT2 inhibitors are not for treating people with type 1 diabetes or for treating diabetic ketoacidosis.
• SGLT2 inhibitors are not prescribed for patients with kidney disease including those on dialysis.

What generic and brand names of SGLT2 inhibitors are available in the US?

Brand and generic names of SGLT2 inhibitors and combination products that contain SGLT2 inhibitors include:

• canagliflozin (Invokana)
• canagliflozin/metformin (Invokamet)
• canagliflozin/metformin extended release (Invokamet XR)
• dapagliflozin (Farxiga)
• dapagliflozin/metformin extended release (Xigduo XR)
• dapagliflozin/saxagliptin (Qtern)
• empagliflozin (Jardiance)
• empagliflozin/linagliptin (Glyxambi)
• empagliflozin/metformin (Synjardy)
• empagliflozin/metformin extended release (Synjardy XR)
• ertugliflozin (Steglatro)
• ertugliflozin/metformin (Segluromet)
• ertugliflozin/sitagliptin (Steglujan)

Do I need a prescription for SGLT2 inhibitors?

Yes

• SGLT2 inhibitors reduce blood glucose by blocking the action of a protein called sodium-glucose co-transporter-2 (SGLT2) in the kidney. This protein is responsible for reabsorbing sugar back into the body from urine. Blocking this protein prevents the kidney from reabsorbing glucose from urine and causes glucose to be removed from the body through urine. This lowers the level of glucose in the blood.
• SGLT2 inhibitors also reduce blood pressure and cause weight loss. In one study, empagliflozin (Jardiance) significantly reduced the risk of death from cardiovascular causes, death from any cause, and the risk of hospitalization for heart failure in people with type 2 diabetes.
• The FDA approved the first SGLT2 inhibitor, canagliflozin (Invokana), in 2013.

WARNING

On Aug. 29, 2018, the FDA issued a warning that cases of a rare but serious infection of the genitals and area around the genitals have been reported with the class of type 2 diabetes medicines called SGLT2 inhibitors. This serious rare infection, called necrotizing fasciitis of the perineum, is also referred to as Fournier’s gangrene.

SGLT2 inhibitors are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine. First approved in 2013, medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. In addition, empagliflozin is approved to lower the risk of death from heart attack and stroke in adults with type 2 diabetes and heart disease. Untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease.

Seek medical attention immediately if you experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell. These symptoms can worsen quickly, so it is important to seek treatment right away.

On May 15, 2015, the FDA informed the public that SGLT2 inhibitors have been associated with increased risk of ketoacidosis in people with diabetes.

Common side effects

The most common side effect of SGLT2 inhibitors include:

• Genital yeast infections in men and women
• Urinary tract infections (UTIs)
• Increased urination
• Kidney problems
• Flu like symptoms
• Constipation
• Nasal congestion
• Urinary discomfort
• Back pain

Serious side effects of SGLT2 inhibitors include:

• Kidney failure
• Hyperkalemia (high levels of potassium in the blood)
• Hypotension (low blood pressure)
• Ketoacidosis
• Increased cholesterol levels
• Serious urinary tract infections
• Increased bladder cancer risk
• Serious allergic reactions
• Low blood glucose (hypoglycemia) when combined with insulin or drugs that increase insulin production
• Dehydration

SGLT2 inhibitors are available as tablets.

• canagliflozin (Invokana): 100, 300 mg tablets
• dapagliflozin (Farxiga): 5, 10 mg tablets
• empagliflozin (Jardiance): 10, 25 mg tablets

• Combining SGLT2 inhibitors with insulin or drugs that increase insulin secretion increases the risk of hypoglycemia.
• Combining SGLT2 inhibitors with diuretics increases the frequency of urination and the risk of dehydration.
• Rifampin, phenytoin, phenobarbital, ritonavir (Norvir) increase the removal of canagliflozin from the body by increasing the action of UDP glucuronosyl transferases (UGT) enzymes. UGT are enzymes that convert chemicals in the body to other types of chemicals that dissolve better in water and are easier to remove from the body. This interaction may reduce the efficacy of canagliflozin. Therefore, the dose of canagliflozin may need to be increased when it is combined with drugs that increase its removal form the body.
• Canagliflozin increases blood levels and the effect of digoxin.
• The prescribing information for dapagliflozin does not list any drug interactions.

SGLT2 inhibitors have not been adequately evaluated in pregnant women. SGLT2 inhibitors affected kidney development and maturation in animals.

It is unknown whether SGLT2 inhibitors are secreted in human breast milk. To avoid any risk to the infant, breastfeeding women should stop either SGLT2 treatment or breastfeeding.