​Invokana & SGLT2 Inhibitors

Approved by the FDA in the Spring of 2013 and marketed heavily thereafter, Canagliflozin AKA Invokana is the first Sodium-Glucose Co-Transporter 2 Inhibitor and most recent drug class on the market to aid Type 2 Diabetics, specifically designed to lower glucose levels. Medical history, lifestyle, allergies, comorbidities, side effects and other drugs being taken are a few factors that depend on whether Invokana is a good match for a Type 2 Diabetic. Ideally Invokana would be prescribed to a patient that is overweight, has high blood pressure and needs glycemic control.

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 emergency process to jettison excess sugar. Invokana is the ONLY type of Type 2 Diabetes drug that goes into an emergency mechanism to deal with excess sugar and the ONLY one to force the kidneys to deal with a process they are not equipped for or use to.

Subsequent Drugs (pill form):

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

Who’s Behind This Drug

  • Mitsubishi Tanabe Pharma Corp
    • Developed in collaboration with Johnson&Johnson
  • Janssen Pharmaceuticals
    • Acquired the licensing agreement with Tanabe for the rights to Invokana in North America, South America, Europe, Middle East, Africa, Australia, New Zealand and part of Asia
    • Wholly owned subsidiary of Johnson&Johnson
  • Johnson&Johnson
    • Developed with Mitsubishi

Benefits of Invokana:

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

Risks of Invokana:

  1. Renal or kidney failure
  2. Cardiovascular risks
  3. Neoplasia
  4. Breast and bladder cancer events
  5. Vaginal irritation and UTI’s in women
  6. Increased risk of bone fracture in elderly patients
  7. Ketoacidosis: On May 15th, 2014 the FDA issued a safety communication regarding a possible link between SGLT2 inhibitors and a potentially life-threatening condition known as ketoacidosis.

What is Ketoacidosis? When the body does not have enough insulin to use sugar for fuel, it breaks down fat instead. As fat breaks down, waste products called ketones build up in the blood and urine, which are poisonous at high concentrations. If left untreated, ketoacidosis can lead to fluid buildup in the brain, heart attack, kidney failure, and death.

The FDA Adverse Event Reporting System identified 20 cases of diabetic ketoacidosis requiring hospitalization from March 2013 to June 2014. These cases were not typical because patients had Type 2 Diabetes and their blood sugar levels measured normal. All patients in the database had been taking the SGLT2 inhibitor for an average of two weeks.

Symptoms of Ketoacidosis:

  • Abdominal pain
  • Confusion
  • Dry skin and mouth
  • Fatigue
  • Flushed face
  • Frequent urination or thirst
  • Fruity-smelling breath
  • Headache
  • Muscle stiffness or aches
  • Nausea and vomiting
  • Rapid breathing
  • Stomach pain

More Facts about Invokana:

  1. This drug is being used off-label as a weight loss medication
  2. Weight loss is caused by diabetic ketoacidosis where body cannibalizes itself to energize itself – It doesn’t metabolize the sugar, it excretes the sugar and blocks its re-absorption
  3. Taking this drug does nothing to promote insulin and may be insufficient to suppress the ketogenic processes – if this happens the patient now has diabetic Ketoacidosis
  4. While it promotes glucagon secretion into the blood, it decreases urinary excretion of ketones (diabetic ketoacidosis) meaning there is more sugar in the blood but without ability to excrete it
  5. A recent FDA Public Health Advisory revealed that the SGL2-inhibitor Invokana is associated with diabetic ketoacidosis in otherwise healthy patients
  6. 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
  7. Invokana uses the image of a heart in their marketing leading consumers to believe using the drug is good for the heart but there is zero evidence of any cardiovascular benefit using Invokana
  8. When asked if reviewers had safety concerns about Invokana’s cardiovascular risk, 8 voted Yes and 7 voted No
  9. FDA approved the drug but required completion of a cardiovascular outcomes study and 4 other post marketing trails, but they are not due until 2017
  10. While the label on Invokana does warn about “impairment in renal function” it does not warn about heart attack, stroke, renal failure or diabetic ketoacidosis
  11. Invokana knew how drug worked – knew all these side effects and went so far as to use the 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.