SGLT2 inhibitors: Uses, common brands, and safety info

People with Type 2 diabetes have many options in terms of medications. One class of drugs used to control Type 2 diabetes is known as sodium-glucose cotransporter 2 inhibitors, or SGLT2 inhibitors. SGLT2 inhibitors are approved by the U.S. Food and Drug Administration (FDA) to lower blood sugar in adults with Type 2 diabetes mellitus. An SGLT2 inhibitor should be used with exercise and diet as part of a diabetes care plan. Drugs in this class are taken by mouth, not by injection.

SGLT2 inhibitors are available as single-ingredient products (see chart below) and combination products with other diabetes drugs like metformin. SGLT2 inhibitors help the kidneys remove sugar from the body by excretion in the urine, lowering blood sugar. SGLT2 inhibitors are indicated for Type 2 diabetes. They are not used in children or people with Type 1 diabetes. 

The chart below lists single-product SGLT2 inhibitors. In this article, we will focus on single-product SGLT2 inhibitors.

Other SGLT2 inhibitors

Below is a list of combination drugs that contain an SGLT2 inhibitor:

• Glyxambi

• Invokamet, Invokamet XR (canagliflozin/metformin)

• Qtern (dapagliflozin/saxagliptin)

• Segluromet (ertugliflozin/metformin)

• Steglujan (ertugliflozin/sitagliptin)

• Synjardy

• Trijardy XR

• Xigduo XR

What are SGLT2 inhibitors?

SGLT2 inhibitors prevent glucose (sugar) from being reabsorbed. SGLT2 inhibitors help the kidneys eliminate sugar in the urine, lowering glucose levels. An SGLT2 inhibitor may be used along with diet and exercise to help lower blood sugar in people with Type 2 diabetes. It may be used alone or with other diabetes medications, depending on the patient.

How do SGLT2 inhibitors work?

The sodium-glucose cotransporter-2 (SGLT2) is in the proximal tubules of the kidneys and reabsorbs about 90% of glucose. The mechanism of action of SGLT2 inhibitor drugs is to help prevent reabsorption, allowing the kidneys to eliminate sugar in the urine. Through this SGLT2 inhibition, blood glucose levels and hemoglobin A1C (HbA1C) levels are lowered from baseline. Blood pressure may decrease slightly as well, and the patient may have a slight weight loss. 

In addition to lowering glucose, other benefits have been found in clinical trials. For example, the EMPA-REG (EMPAgliflozin Removal of Excess of Glucose) OUTCOME study found that patients who took Jardiance had a 38% relative risk reduction in heart-related deaths. This may benefit patients who have had a previous stroke or heart attack.

What are SGLT2 inhibitors used for?

SGLT2 inhibitors are indicated:

• to improve blood sugar control in patients with Type 2 diabetes, in combination with diet and exercise. 

• to lower the risk of major cardiovascular events in adults with Type 2 diabetes and established cardiovascular disease.

• to reduce the risk of end-stage kidney disease, doubling of serum creatinine levels, heart-related death, and heart failure hospitalization in adults with Type 2 diabetes and diabetic kidney disease with albuminuria (excess albumin in the urine).

SGLT2 inhibitors may be beneficial in patients who are obese and/or who have high blood pressure because they can slightly decrease weight and blood pressure.

Several clinical trials have studied SGLT2 inhibitors in patients with diabetes and other risk factors (such as smoking or hypertension) and have been published in medical journals such as Circulation, JAMA, and the New England Journal of Medicine (N Engl J Med). A meta-analysis of these trials found that SGLT2 inhibitors improve blood sugar control and also have the other benefits listed above, such as improved kidney and cardiovascular outcomes. 

SGLT2 inhibitors are not indicated for children or patients with Type 1 diabetes.

SGLT2 inhibitors are being studied (but not currently indicated) in the treatment of:

• Non-alcoholic fatty liver disease

• Obesity 

• Early-stage lung adenocarcinoma

Who can take SGLT2 inhibitors?

Men

Men can take an SGLT2 inhibitor, provided there is an appropriate indication and that there is no contraindication (see below).

Women

Women can take an SGLT2 inhibitor, provided there is an appropriate indication and that there is no contraindication (see below).

Women who are pregnant, planning to become pregnant, or breastfeeding should talk to their doctor about an alternative medication. SGLT2 inhibitors can cause harm to an unborn baby, especially in the second and third trimesters. SGLT2 inhibitors are not recommended while breastfeeding. 

Older adults

Older adults should consult a healthcare professional about the use of SGLT2 inhibitors. 

Patients 65 years and older are likely to have a higher rate of side effects, including low blood pressure, dizziness, orthostatic hypotension (blood pressure falls when sitting up or standing), fainting, and dehydration. 

There is a more noticeable increase in side effects in patients 75 years of age and older. 

Children

Currently, children cannot take an SGLT2 inhibitor. SGLT2 inhibitors have not been studied in children.

Are SGLT2 inhibitors safe?

Recalls

No recalls were found. Other drug safety communications about SGLT2 inhibitors can be found on the fda.gov website. 

Restrictions

Do not take an SGLT2 inhibitor if:

• you have had an allergic reaction to an SGLT2 inhibitor.

• you have severe kidney impairment/impaired renal function/are on dialysis.

See information on pregnancy and breastfeeding below.

Can you take SGLT2 inhibitors while pregnant or breastfeeding?

SGLT2 inhibitors have not been studied in pregnant women, but based on animal data, they may cause harm to an unborn baby. If you are pregnant or planning to become pregnant, consult your doctor before taking an SGLT2 inhibitor. 

If you are already taking an SGLT2 inhibitor and find out that you are pregnant, consult your healthcare professional right away. 

SGLT2 inhibitors are not recommended for breastfeeding women. Consult your healthcare provider for medical guidance.

Are SGLT2 inhibitors controlled substances?

No. SGLT2 inhibitors are not controlled substances.

Common SGLT2 inhibitors side effects

The most common side effects of SGLT2 inhibitors are:

• High levels of potassium (hyperkalemia)

• Increased cholesterol

• Increased magnesium and phosphate levels

• Low blood sugar

• Urinary tract infections

• Genital infections

• Increased urination

• Vulvar and vaginal itching

• Thirst 

• Orthostatic hypotension 

• Constipation 

• Nausea 

• Tiredness 

• Lower limb amputation risk (Invokana)

Rare but serious side effects may occur. These may include: 

• Allergic reactions, including anaphylaxis

• Acute kidney injury

• Ketoacidosis

• Serious urinary tract infection

• Pancreatitis

• Loss of bone density

• Fractures (Invokana)

• Fournier’s gangrene

• Risk of renal cell cancer

Warnings/severe side effects:

• Necrotizing fasciitis: SGLT2 inhibitors may cause a rare but serious bacterial infection around the anus and genitals (perineum). This is called Fournier’s gangrene. It can lead to hospitalization and can be fatal. Get emergency medical attention right away if you have fever, weakness, tiredness, and have pain, redness, or swelling around the anus and genitals. Fournier’s gangrene can occur with any SGLT2 inhibitor.

• Fungal genital tract infections: There is a higher risk of fungal genital tract infections in patients with Type 2 diabetes. SGLT2 inhibitors may increase the risk for these infections, usually in the first 6 months of treatment. If you have an odor, discharge, pain, rash, redness, or swelling in the genital area, contact your doctor. Fungal genital tract infections can occur with any SGLT2 inhibitor.

• Amputations: There is an increased risk of lower limb amputation (leg, toe, foot) with Invokana. Contact your doctor right away if you have any pain, tenderness, sores, ulcers, or infections in the leg or foot.

• Urinary tract infections (UTIs): SGLT2 inhibitors may cause urinary tract infections, which may be severe and lead to hospitalization. Contact your doctor right away if you experience frequent urination, burning while urinating, or blood in the urine. UTIs can occur with any SGLT2 inhibitor.

• Dehydration: SGLT2 inhibitors may cause dehydration. You may feel dizzy, lightheaded, or weak, especially when standing up. Talk to your doctor about an appropriate amount of fluid intake. You may be at higher risk if you take certain medications, like diuretics. Dehydration can occur with any SGLT2 inhibitor.

• Bone fractures: Invokana may be associated with an increased risk of bone fractures.

• Electrolyte imbalance: SGLT2 inhibitors may slightly affect electrolyte levels.

• Diabetic ketoacidosis (DKA): SGLT2 inhibitors may increase the risk of DKA, in which the body makes excess blood acids (ketones). Contact your doctor if you have nausea, vomiting, stomach pain, tiredness, or trouble breathing. Check your ketones if you are able to. DKA can occur with any SGLT2 inhibitor.

• Cholesterol levels: SGLT2 inhibitors may slightly increase HDL and LDL levels.

• Hypoglycemia (low blood sugar): If you take an SGLT2 inhibitor with another diabetes drug or insulin, there is a higher risk of hypoglycemia. Symptoms may include confusion, shaking, dizziness, hunger, weakness, irritability, sweating, and/or headache. 

Although allergic reactions are rare, if you have symptoms such as hives, difficulty breathing, or swelling of the face, lips, or tongue, get emergency medical help right away. 

Before taking an SGLT2 inhibitor, tell your doctor about your medical history and medical conditions. Tell your doctor about all of the medications you take, including prescription drugs, OTC medicines, and vitamins or supplements. Your doctor will ensure drug safety by screening for drug interactions.

This is not a complete list of side effects. Other side effects may occur. Consult your doctor for a complete list of side effects. 

How much do SGLT2 inhibitors cost?

Currently, all of the SGLT2 inhibitors are only available in the brand name form. There are no generics currently available for SGLT2 inhibitors. Insurance coverage varies by plan. Consult your insurance or Medicare prescription plan provider for up-to-date coverage information. 

You can also check the manufacturer’s websites for rebates, copay programs, or savings plans. For example, Jardiance is made by Boehringer Ingelheim Pharmaceuticals, Inc., so you can check the official Jardiance website to see if Boehringer Ingelheim offers any discounts on Jardiance. 

You can always save money by using free SingleCare cards and coupons. People who use SingleCare cards and coupons save up to 80% on their prescriptions and refills.