More than 29 million people in the United States currently have diabetes, and another 86 million pre-diabetics are on the cusp of developing the disease. New investigations into the safety of the heavily prescribed medication uncovered a long list of Invokana side effects.


The Truth

Studies + Science

Regulation Recap

The Next Steps
Invokana can cause ketoacidosis, lead to limb amputations and spark other serious side effects.Studies show that Invokana increases the risk of ketoacidosis, a serious medical emergency.The FDA issued five alerts about the safety of Invokana and the SGLT2 inhibitor class as a whole.Recent FDA investigations have increased the number of resources available to people injured by Invokana.

 

Dangers For Diabetics

Invokana is used for the treatment of type II diabetes, which occurs when the body cannot effectively use insulin. The medication’s active ingredient, canagliflozin, works with the kidneys to deposit excess glucose in urine, maintain safe blood sugar levels and keep patients from going into diabetic shock.

Manufactured by Johnson & Johnson, the sodium-glucose cotransporter 2 (SGLT2) inhibitor falls into the category of new-age treatments. Doctors can prescribe the drug in 100mg or 300mg doses that are compressed in a once-daily tablet. The majority of Invokana users begin at the lowest level.

Invokana is the number one prescribed SGLT2 inhibitor in the United States. Growing concerns about the safety of the popular drug prompted the Food and Drug Administration (FDA) to launch a number of safety investigations, which linked Invokana to ketoacidosis, broken bones, cardiovascular complications, lower limb amputations and irrevocable kidney damage.

As health professionals dig deeper to uncover the long-term Invokana side effects, this contemporary class of diabetes drugs generates billions for Big Pharma’s multi-platform businesses.

Studies + Science

A large portion of scientific research on diabetes drugs has been FDA-mandated and conducted by manufacturers, while other data comes from adverse event reports. Millions of Americans currently have or will develop diabetes, which elevates understanding the disease and treatment options to a high priority.

Diabetes drugs are divided into various classes, with SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors at the forefront. While both medications improve the function of insulin systems, each drug targets and blocks a different hormone.

SGLT2 inhibitors: Brand name | Active ingredient(s)

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

DPP-4 inhibitors prevent the DPP-4 enzyme from inactivating essential gut-balancing hormones, whereas SGLT2 inhibitors work with the kidneys to unload excess glucose in urine. SGLT2 is the human protein responsible for 90 percent of glucose reabsorption.

SGLT2 inhibitors have three main functions:

  • to block the reabsorption of glucose in the kidney
  • to increase glucose excretion
  • to lower blood glucose levels

What is ketoacidosis?

Ketoacidosis is a condition that can quietly sneak up on diabetics and quickly spin their diabetes out of control. Ketoacidosis is a medical emergency that can lead to a diabetic coma, require hospitalization and sometimes cause death.

  • When the body isn’t receiving enough carbohydrates, it burns fat to store and use as fuel. Ketosis occurs when this process causes poisonous compounds called ketones to develop in the blood.
  • Acidosis is increased acidity in the blood caused by the ketones, which occurs when the body doesn’t have enough insulin to use glucose as its primary energy source.

Ketoacidosis has been linked to kidney problems, urinary tract infections, weight loss, vomiting, dehydration, confusion, fatigue, and abdominal pain. When the condition becomes serious, treatment is often administered in a hospital setting and may include intravenous fluids, insulin and glucose.

Through the FDA Adverse Event Reporting System (FAERS) database, the agency pinpointed 73 cases of ketoacidosis caused by SGLT2 inhibitors. The agency only included cases reported from March 2013 to May 2015, asserting that “there are likely additional cases about which we are unaware.”

Ketoacidosis is a common side effect associated with the diabetes drug Invokana, but it isn’t the only one. Additional Invokana side effects include bone fractures, cardiovascular complications, genital infections and amputations.

Bone Fractures

Data illustrates that Invokana can speed up the loss of bone density, resulting in osteoporosis. A government-mandated Johnson & Johnson study showed accelerated deterioration of spine and hip bones after two years of using the drug. The post-market safety study involved nine clinical trials and more than 700 geriatric patients who took Invokana for an average of 85 weeks.

“The additional data confirm the finding that fractures occur more frequently with canagliflozin than placebo,” the study authors write. “Fractures can occur as early as 12 weeks after starting the drug. In the clinical trials, when trauma occurred prior to a fracture, it was usually minor, such as falling from no more than standing height.”

While some patients didn’t notice the effects of Invokana for an extended period, few experienced bone fractures within three months of use. Issues with bone density were found to be most common in postmenopausal women, and generally occurred in the hips and lower spine.

Kidney Injuries

From March 29, 2013 to October 19, 2015, the FDA found 101 cases of acute kidney injury. The organization identified 73 injuries caused by Invokana. The FDA Adverse Event Reporting System (FAERS) database illustrated that 96 out of 101 people had to be hospitalized, with 22 requiring intensive care. Out of the four people who died, two experienced cardiac complications.

Fifteen patients received dialysis, and of these, 3 patients had a history of chronic kidney disease or previous acute kidney injury. In 58 cases, the Invokana patient developed acute kidney injury occurred within one month or less. More than half of these individuals were 60 years or younger.

Cardiac Complications

In addition to the two deaths discovered in the FAERS reporting system, the manufacturer’s post-marketing clinical trials also uncovered a high hazard ratio for cardiac events. Some patients may experience a heart attack or stroke within the first 30 days of treatment.

Urinary Tract and Yeast Infections

The FDA used the FAERS database to detect 19 urinary tract infections, linked to the use of SGLT2 inhibitors, that led to life-threatening blood and kidney infections. The infections were reported from March 2013 through October 2014, with each infection requiring hospitalization. Some patients have infections that were so severe they were admitted to an intensive care unit, or placed on dialysis to stop their kidneys from failing.

Leg and Foot Amputations

An ongoing clinical trial, known as Canagliflozin Cardiovascular Assessment Study (CANVAS), found people taking Invokana were twice as likely to need their leg or foot amputated. CANVAS researchers studied patients for more than one year. The researchers developed the following amputation risk ratio:

  • 7 out of every 1,000 patients treated with 100 mg daily of canagliflozin
  • 5 out of every 1,000 patients treated with 300 mg daily of canagliflozin
  • 3 out of every 1,000 patients treated with placebo

 

Regulation Recap

Approved by the FDA in March 2013, Invokana was marketed as a new, first-class solution to controlling diabetes. Today, Invokana approval only extends to type II diabetes because the drug lacks an established safety profile for type I treatments.

Canagliflozin, alongside dapagliflozin and empagliflozin, are classified as SGLT2 inhibitors. Although SGLT2 inhibitors are the new kids on the block, they’ve dominated the market.

But a high number of adverse event reports sparked concerns about the safety of the drug, prompting the FDA to take action and issue five safety alerts.

Information on SGLT2 Inhibitors (via fda.gov)

  • FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR)
    6/14/2016
  • FDA Drug Safety Communication: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate
    5-18-2016
  • FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections
    12-4-2015
  • FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density
    9-10-2015
  • FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood
    5-15-2015

2015 Safety Communications

From March 2013 to June 2014, the FDA documented 20 cases of acidosis in patients who had been using the drug for about two weeks. After many of these patients ended up hospitalized or in an emergency room, the FDA reinvestigated the safety of the drug.

In May 2015, the FDA issued a warning about Invokana’s connection to ketoacidosis. The regulatory body has received hundreds of adverse event reports since.

In September 2015, the FDA extended Invokana’s Warning and Precaution and Adverse Reactions sections to include the loss of bone density. The FDA has ordered the manufacturer to add the risk of bone fractures to the labeling.

The FDA acknowledged that the labeling on Invokana and Invokana-metformin combination drug Invokamet already includes the risk of bone fractures, but the recent addition comes from new studies that show bone issues will occur more frequently.

In December 2015, the FDA notified the public about SGLT2 drugs causing too much acid in the blood and serious urinary tract infections. The announcement came after the FDA identified 73 cases of ketoacidosis and 19 life-threatening urinary tract infections.

The FDA released information from the CANVAS clinical trial to illustrate the risk of amputation linked to Invokana, which mostly affects the toes. The agency continues to investigate the particular side effect.

Most recently, the FDA extended an additional kidney-related public announcement in June 2016, linking Invokana to acute kidney injury. Acute kidney occurs when the kidneys stop filtering waste, which then builds up in the body.

“We urge health care professionals and patients to report side effects involving canagliflozin, dapagliflozin, or other medicines to the FDA MedWatch program,” the FDA wrote.

A Major Moneymaker

One out of three people will develop type II diabetes in their lifetime, which makes the manufacturing of diabetes medications extremely profitable. The amount of drugs on the market has created a fiercely competitive atmosphere. Adding additional risks to warning labels could seriously affect reputation, which drives down profits for the drug manufacturer.

While the FDA is in the process of assessing the danger of new-age diabetes drugs, ProPublica reported that Johnson & Johnson spent over $7 million on the drug’s endorsement and marketing. Insurance systems like Medicare also contribute to the frequency of their prescription.

Since the drugs were approved in 2013, Invokana and Invokamet have been bringing in big bucks for Johnson & Johnson. The pair brought in a total $318 million in the second quarter and hit $596 million in the first half of 2015. Their advertising strategy has led Invokana to be one of the highest earning drugs of its class.

Rising Cost of Diabetes Care

Diabetes is a complex condition that requires daily attention. As more and more Americans develop the disease, the cost of general care and support for side effects only grows.

“The economic burden associated with diagnosed and undiagnosed diabetes, gestational diabetes mellitus, and prediabetes was estimated to be 48% higher than that reported in 2007,” according to the journal Diabetes Care. “For 2012, the estimated total burden exceeded $322 billion, comprising $244 billion in excess medical costs and $78 billion in reduced productivity.”

Future For Diabetics

More than 1.7 million people over the age of 20 were diagnosed with diabetes in 2012. The CDC now estimates that as many as 1 in 3 U.S. adults could have diabetes by 2050.

While the FDA continues to investigate, many diabetics may be prescribed Invokana. Diabetic patients using the SGLT2 inhibitors could face broken bones, amputated limbs and ketoacidosis emergencies. Some will spend weeks in the hospital recovering from a cardiac problem or critical infection.

Actionable Outreach

The FDA has become increasingly aware of the complications, which damages and degrades vital parts of the human body. As the agency works to inform the public about the dangers, support for individuals surviving Invokana side effects continues to grow.

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