Sodium-glucose cotransporter-2 inhibitors, also called gliflozin drugs, are a class of prescription medications that help lower blood sugar in adults with type 2 diabetes mellitus. The U.S. Food and Drug Administration (FDA) has approved more than a half dozen SGLT2 inhibitors for use with diet and exercise to manage blood glucose levels.

In addition to treating diabetes, SGLT2 inhibitors have shown potential benefits related to other diseases and health conditions. Top among these are improvements in patients with cardiovascular problems, including those who have previously experienced heart failure. SGLT2 inhibitors have also been positively associated with weight loss and lower blood pressure.

What Consumers Should Know About SGLT-2 Inhibitors

Gliflozin drugs are a new class of drugs compared to other diabetes treatments, such as metformin and insulin. The first SGLT2 inhibitor, canagliflozin (Invokana), was approved in 2013, with several others receiving approval over the next year or two. As a result, health professionals and researchers are still learning about some of the long-term adverse effects of these drugs.

Dangerous SGLT2 Side Effects

Some SGLT2 inhibitors have been associated with severe, and potentially deadly, side effects. While many patients will benefit from taking gliflozins, it is important to talk with your doctor about the risk of developing one of these complications at your checkup.

Fournier’s gangrene (necrotizing fasciitis) – In August 2018, the FDA issued a safety warning about the risk of developing a painful and possibly deadly infection of the genitals and surrounding area. Twelve cases of necrotizing fasciitis, commonly called “flesh-eating bacteria,” were found in a span of 5 years in patients who took SGLT2 inhibitors, versus only six cases over 30 years with other type 2 diabetes drugs.

Lower Body Amputation – Diabetes can cause people to have severe foot problems due to poor circulation, nerve damage, and peripheral arterial disease, possibly requiring a partial or complete amputation. A study by the FDA found that people who took canagliflozin (Invokana) required leg and foot amputations twice as often as those who took a placebo. The European Medicines Agency has warned that all SGLT2 inhibitors may increase the risk of lower-limb amputations, but some studies show that risk to be applicable only to Invokana.

Diabetic Ketoacidosis – This life-threatening diabetic complication occurs when high levels of blood acids (ketones) accumulate in the bloodstream. If left untreated, diabetic ketoacidosis can cause dehydration, brain swelling, coma, and even death. Diabetic ketoacidosis is known to be a risk with canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance).

Kidney Failure – While some studies have indicated that SGLT2 inhibitors may help slow the progression of kidney damage (diabetic nephropathy), others have shown that gliflozin drugs are potentially dangerous for people with advanced renal disease. For example, a review of reports by the FDA in 2016 showed that people who take canagliflozin (Invokana) or dapagliflozin (Farxiga) have a higher risk of severe kidney disease (renal failure), which can require hospitalization and dialysis. Because of inconsistent findings, a number of researchers have called for more clinical trials on the potential kidney-related hazards of SGLT2 inhibitors.

Acute Pancreatitis – Although rare, some SGLT2 inhibitors can lead to a sudden inflammation of the pancreas, an abdominal organ that produces insulin and other hormones. Researchers believe this happens because of the drug’s diuretic (dehydrating) effect, and it can lead to a variety of other health problems or even death.

Cancer – There is some evidence that SGLT2 inhibitors could increase the risk of certain forms of cancer, including bladder cancer and breast cancer. However, given the short amount of time that SGLT2 inhibitors have been available to the public, many researchers have called for more clinical trials to research any potential links.

SGLT2 Inhibitors List

Generic NamesBrand NamesDrug Companies
Canagliflozin
  • Invokana
  • Invokamet
  • Sulisent
  • Mitsubishi Tanabe Pharma
  • Janssen Pharmaceuticals (Johnson & Johnson)
Dapagliflozin
  • Farxiga (US), Forxiga (Europe)
  • Xigduo XR
  • Qtern
  • Bristol-Myers Squibb
  • AstraZeneca
Empagliflozin
  • Jardiance
  • Synjardy (Jardiance + metformin)
  • Boehringer Ingelheim
  • Eli Lilly and Company
Ertugliflozin
  • Steglatro
  • Merck
  • Pfizer

How SGLT2 Inhibitors Work

Invokana and other SGLT2 inhibitors work by blocking the sodium-glucose cotransporter 2 (SGLT2) protein, which facilitates glucose reabsorption. Reabsorption normally happens in the kidneys, but SGLT2 inhibitors prevent that process from taking place, causing glucose excretion in the urine.

Invokana and other SGLT2 inhibitors are prescribed with a low-sugar diet and exercise. It is not meant to control diabetes on its own – patients still need to maintain a healthy lifestyle while taking the drug. Also, the drug is only effective against type 2 (adult onset) diabetes; it is not prescribed to treat type 1 diabetes.

While some other SGLT2 drugs have been developed and are currently in use in other parts of the world, such as ipragliflozin and tofogliflozin in Japan, only the four listed above have been approved by the FDA for use in the United States.

Common SGLT2 Side Effects

In addition to the severe side effects mentioned above, gliflozin drugs can lead to an increased risk of the following medical conditions:

Hypoglycemia: Because SGLT2 inhibitors work by removing glucose from the blood, there is a risk that blood sugar will become too low.

Urinary tract infection: All SGLT2 inhibitors are associated with an increased risk of urinary tract infection, which could lead to secondary symptoms such as a burning sensation while urinating, cloudy urine, pelvic pain, and back pain.

Fungal Infections: An increase in the risk of developing yeast infection in women and balanitis in men are common while taking SGLT2 inhibitors. Secondary symptoms may include itching, pain, odor, discharge, or redness and swelling around the genitals. Those who have had fungal infections in the past are more susceptible.

Dehydration: SGLT2 inhibitors can have a diuretic effect, which can cause increased urination and lead to dehydration. Related side effects include dizziness, lightheadedness, fainting, weakness, and low blood pressure.

High LDL Cholesterol: All SGLT2 inhibitors can increase the levels of low-density lipoprotein cholesterol (LDL cholesterol) in the bloodstream.

SGLT2 Inhibitor Lawsuits

Some manufacturers of gliflozin drugs have found themselves as defendants in lawsuits by patients, or their survivors, who have suffered from severe side effects. Two of these diabetes drugs have had enough lawsuits to be consolidated in federal courts under multidistrict litigation. More lawsuits for these and other SGLT2 inhibitors have been filed in state courts, as well.

Federal MDLs for SGLT2 Inhibitors

  • Invokana (canagliflozin) – MDL 2750: 1,036 active lawsuits as of August 15, 2018
  • Farxiga (dapagliflozin) – MDL 2776: 50 active lawsuits as of August 15, 2018

If you or a loved one has experienced a drastic side effect of Invokana or another SGLT2 inhibitor, you should talk to an attorney right away to understand your legal rights.