SGLT-2 inhibitors are a class of diabetes drugs used to treat type 2 diabetes and, often off-label, type 1 diabetes. These drugs work by preventing your body from re-absorbing sugar into your bloodstream and instead flush it out when you urinate. SGLT-2 medications are taken orally, typically daily.

This drug has an interesting history. The compound was first discovered in the 1800s when someone noticed that if dogs urinate at the bark of a certain tree, ants would be attracted to that dog’s urine. The dog’s urine was sweet. One and a half centuries later, we have a new diabetes treatment!

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a relatively new class of prescription drugs which are FDA approved for type 2 diabetes to use in combination with diet and exercise to help lower blood sugar levels.

Medications in this class include:

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

These are available as single-ingredient drugs or in combination with other diabetes medications. The combinations currently available are:

• canagliflozin and metformin (Invokamet)
• dapagliflozin and metformin extended-release (Xigduo XR)
• empagliflozin and linagliptin (Glyxambi)

How do SGLT2 Inhibitors Work?

SGLT2 is a protein humans have which helps glucose reabsorb in the kidneys. The SGLT2 protein is responsible for 90% of the glucose reabsorption in the proximal renal tube.

An SGLT2 inhibitor stops the reabsorption of glucose in the kidneys and the extra sugar is excreted into the urine. This helps to lower blood sugar levels. Below is a graphic that shows an SGLT2 inhibitor does this:

Side Effects of SGLT2 Inhibitors

The FDA states that “The safety and efficacy of SGLT2 inhibitors have not been established in patients with type 1 diabetes, and FDA has not approved them for use in these patients.” Studies have been indicating patients with type 1 diabetes may be able to use SGLT2 inhibitors safely, however.

Side effects of SGLT2 inhibitors, as reported by the FDA include:

• acidosis
• dehydration
• kidney problems
• low blood sugar when combined with other diabetes medications
• elevated blood cholesterol
• yeast infections in men and women

Warnings from the FDA

The FDA has issued a strengthened warning for canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). The warning is for acute kidney injury and they add the following recommendations to help lower this risk:

“Patients should seek medical attention immediately if they experience signs and symptoms of acute kidney injury. This is a serious condition in which the kidneys suddenly stop working, causing dangerous levels of wastes to build up in the body. Signs and symptoms of acute kidney injury may include decreased urine or swelling in the legs or feet. Patients should not stop taking their medicine without first talking to their health care professionals. Doing so can lead to uncontrolled blood sugar levels that can be harmful.”

The FDA has also issued a warning for any SGTL2 inhibitor stating it may lead to diabetic ketoacidosis (DKA).

It is especially helpful when taking a medication to keep a journal of when you take something and how much you took. Include your symptoms and blood sugar readings in order to be able to help you and your healthcare provider decide whether or not a medication is working safely for you.

If you live in the USA and have experienced a serious side effect, you or your doctor may send a report to the FDA’s MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

SLGT-2 Inhibitors for Type 1 Diabetes

diaTribe shares the following advice from Dr. Anne Peters, who helped author the study that led to the warning on SGLT-2 inhibitors.

In individuals with type 1 diabetes who are using the drug off-label, it is best to work out a plan for safe use of the medication with a health care provider. Dr. Peters has patients temporarily hold the drug if unusual activity will be occurring during the day (e.g., travel, increased exercise, or a person feels unwell). Her patients with type 1 diabetes test ketones a week or two before starting the SGLT-2 inhibitor to obtain a baseline ketone level, then test urine ketones every morning while on the drug. If ketone levels are moderate to large, Dr. Peters recommends stopping use of the drug that day until the ketones clear. Finally, her patients with type 1 or type 2 diabetes stop the drug for three days before any elective surgery.

glycemic diabetic ketoacidosis.”