​Invokana & SGLT2 Inhibitors

SGLT2 Inhibitors: Diabetic Medications Linked to DKA, AKI, and Amputations.

Approved by the FDA in the Spring of 2013 and marketed heavily thereafter, Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors (Invokana, Farxiga, Jardiance, etc.) are one of the most recent types of drugs put on the market to aid Type 2 Diabetics, specifically designed to lower glucose levels. However, even though this medication has only been available on the market for a handful of years, within this time span it has already come to be associated with causing numerous serious injuries in patients, including diabetic ketoacidosis (DKA), acute kidney injury (AKI), and amputation.

How SGLT2 Inhibitors Work

The idea behind prescribing SGLT2 Inhibitors is to lower blood sugar in adults with Type 2 Diabetes. SGLT2 is a protein that prevents the metabolizing of sugar (blocking 90% of sugar from reabsorbing) and uses the body’s biological emergency response to jettison excess sugar.

SGLT2s are the ONLY type of Type 2 Diabetes drug (“antidiabetic”) that catalyze an emergency mechanism in the patient’s system, triggering the kidneys to expel excess sugar in a patient’s body. This mechanism forces a patient’s kidneys to work harder to filter large amounts of sugar from a patient’s blood; however, without SGLT2, this sugar could have been safely metabolized without additional strain on the kidneys. As is, this extra filtration of sugar puts immense strain on the kidneys, which leads to many of the injuries discussed below.

SGLT2 Inhibitor Drugs & Their Manufacturers: 

Types of SGLT2 Inhibitors:

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

SGLT2 Manufacturers:

  • Janssen Pharmaceutical
  • Licensed to market Invokana, Invokamet, and Invokamet XR
  • Subsidiary of Johnson & Johnson
  • Eli Lilly and Company
  • Developed Jardiance and Glyxambi (in collaboration with Boehringer Ingelheim).
  • AstraZeneca
  • Developed Farxiga, Xigduo, and Xigduo XR with Bristol-Myers Squibb

Alleged Benefits of SGLT Inhibitors:

  • Lowers blood sugar and reduces levels of glycated hemoglobin in patients that cannot take Metformin
  • Allows rapid weight loss since patients can pass up to 300 calories of sugar a day

Risks of SGLT2 Inhibitors:

Diabetic Ketoacidosis (DKA) – This occurs when the body does not have enough insulin to use sugar for fuel, it breaks down fat instead. As fats break down, acidic waste products called ketones build up in the blood and urine, which are poisonous at high concentrations

December 04, 2015: The FDA ordered a label change to include warnings about DKA and UTIs for all SGLT2 medications listed above. (https://www.fda.gov/Drugs/DrugSafety/ucm475463.htm)

Symptoms of DKA:

  • Abdominal/stomach pain
  • Confusion
  • Dry skin and mouth
  • Fatigue
  • Frequent urination or thirst
  • Fruity-smelling breath
  • Headache
  • Nausea and vomiting
  • Rapid breathing

Acute Kidney Injury (AKI) – Also known as acute renal failure, this injury is a type of rapid-onset kidney failure that causes a build-up of waste product in your blood and makes it hard for your kidneys to keep the right balance of fluid in your body.

June 14, 2016: The FDA issued a safety communication to strengthen the existing warning about the risk of acute kidney injuries for those taking SGTL2 Inhibitors. (https://www.fda.gov/Drugs/DrugSafety/ucm505860.htm)

Severe urinary tract infections (UTIs) requiring hospitalization – A UTI is an infection of the urethra that can travel up to the bladder, and if untreated, eventually the kidneys. This interrupts the system for removing urine and can lead to urosepsis and other serious complications.

December 04, 2015: The FDA ordered a label change to include warnings about DKA and UTIs for all SGLT2 medications listed above. (https://www.fda.gov/Drugs/DrugSafety/ucm475463.htm)


May 16, 2017: Based on data from two large clinical trials, the FDA determined that patients who use Invokana, Invokamet, or Invokamet XR are at an increased risk of having to undergo foot and leg amputations. The study indicates that patients taking these medications are twice as likely to suffer complications necessitating one or more such amputations than are patients who use other/different antidiabetic medications. In response to these findings, the FDA now requires the infamous Boxed Warning advising of the risk of amputation be included on the label for Invokana. (https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm)

More Facts about Invokana and other SGLT2 medication:

  1. This type of drug is being used off-label as a weight loss medication
  2. Invokana advertises that it “works with your kidneys to help you lose sugar through the process of urination” but recent studies expose this misleading conception since part of the drugs design is to allow a high level of glucose to enter the kidneys
  3. The FDA approved the drug but was and is concerned about the possible cardiac side-effects of SGLT2s; the FDA is requiring additional cardiovascular trials before they can rule out the risk or cardiac dangers associated with these medications.
  4. Pharmaceutical manufacturers knew how these drugs worked – they had reason to be aware of all these side effects and still went on to use the possibility of weight loss as a marketing ploy.

Since the drugs are so new, more information from ongoing clinical trials will come to light in the years to follow. If some of the adverse event associations turn out to be significant, then the manufacturers of these drugs could be held liable for failing to conduct appropriate safety trials before releasing these medications to the public and for failing to warn patients of serious risks from their products’ use.