Diabetes Medicine: SGLT2 Inhibitors

So far, the diabetes medicines that we’ve looked at work on the pancreas, the muscles, the liver, and the gut. If anything, the fact that these medicines target and affect many different organ systems in the body tells us just how far-reaching diabetes is. In fact, diabetes affects nearly every system in the body, including the brain, the skin, the mouth, and even your hearing!

The medicines highlighted this week are from the newest class of diabetes drugs to hit the scene: SGLT2 inhibitors.


What are SGLT2 inhibitors?
To understand how this class of medicines work, it helps to know what SGLT2 is. The kidneys filter about 45 gallons of blood each day. Most of this glucose in this blood is reabsorbed by the kidneys by a protein called sodium-glucose cotransporter-2 (SGLT2). If you have diabetes, this is not what you want to have happen; you want the glucose to leave your body, not be reabsorbed. Now, there is a class of medicine for that, called SGLT2 inhibitors.

Canagliflozin (brand name Invokana) was the first drug in this class to be approved, which occurred in 2013. Since then, dapagliflozin (Farxiga) and empagliflozin (Jardiance) have been approved. These drugs work by blocking the action of the SGLT2 protein, preventing the kidneys from reabsorbing glucose back into the bloodstream.

The result is that the kidneys are able to excrete more glucose through the urine, thus lowering blood glucose levels.

Canagliflozin is also available in combination with metformin in a drug called Invokamet, while dapagliflozin is combined with metformin extended-release in the medicine Xigduo XR. Empagliflozin is available in a combination drug with linagliptin (Tradjenta, a DPP-4 inhibitor) called Glyxambi. In addition, SGLT2 inhibitors, also called gliflozins, can be taken along with sulfonylureas, pioglitazone (Actos), and insulin.

How are SGLT2 inhibitors taken?
These medicines are in pill form, and are taken once a day, usually in the morning. They come in different doses; the dose may be increased depending on how well your kidneys are working.

What are the side effects of SGLT2 inhibitors?
It’s important to realize that this new class of drugs is completely different from the diabetes pills that you may be familiar with, as they work on the kidneys. Because they work to remove glucose from the body, one of the side effects to watch out for is urinary tract and genital infections (for example, yeast infections) in both men and women. Women are more likely to experience these side effects. Lower your risk of these infections by drinking plenty of fluids and by practicing good hygiene.

You might also urinate more than usual (especially during the night) when taking one of these drugs. This is normal and is a response to the body’s effort to rid itself of extra glucose. Because of this, the risk for dehydration goes up, so make sure to drink enough fluids.

Other possible side effects include high potassium levels, increased cholesterol, kidney problems, and low blood sugar (if you take this drug with insulin or a sulfonylurea).

One of the more “positive” side effects of SGLT2 inhibitors is weight loss. Remember that glucose contains calories; as your body rids itself of excess glucose, it’s removing calories (often hundreds of them) at the same time, which may lead to some weight loss.

What else should you know about SGLT2 inhibitors?
You may have low blood pressure when taking this medicine — especially when you stand up — particularly if you are an older adult and/or have kidney problems.

If you become pregnant while taking one of these drugs, let your doctor know. SGLT2 inhibitors are not approved for use in pregnant or nursing women or in children.

Anyone with severe chronic kidney disease or active bladder cancer should avoid taking SGLT2 inhibitors.

Recently, reports of diabetic ketoacidosis (DKA) have been noted while taking SGLT2 inhibitors. DKA is a very serious and potentially fatal condition that occurs mostly in people who have Type 1 diabetes. However, it may occur, although rarely, in those with Type 2 diabetes, and the risk may be higher if you’re taking one of these drugs. Illness, not taking your insulin as prescribed, and dehydration are risk factors for DKA.

Drink plenty of fluids when taking these medicines. Aim for at least 8 cups of fluid each day, even if you’re not thirsty. Talk with your doctor about the safety of taking one of these drugs if you are under fluid restriction therapy.

More on diabetes medicines next week!

Diabetes can affect the brain, but there are steps you can take to keep your memory alive. Bookmark DiabetesSelfManagement.com and tune in tomorrow to learn more from Type 2 diabetes veteran Martha Zimmer!

  • As a recommendation is based on expert opinion. We have Drugs like SGLT2 inhibitors, GLP agonists, DPP4 inhibitors, Acarbose and ‘n’ no. Of combinations. From sulfonylureas to Pramlintide. After exhausting all of these combinations, we think of insulin. While insulin is used in combination with oral medications, but a type 2 diabetic should stay on metformin or switch to insulin injections?

    • acampbell

      Hi Partha,
      The decision to switch to insulin is generally made based on the person’s ability to achieve and sustain his/her A1C and glucose goals. Many doctors try 2 or 3 different types of diabetes pills or non-insulin injectable medicines before putting someone on insulin, often because a person may be afraid of starting insulin for various reasons.