Diabetes causes high levels of sugar in the blood, meaning wounds can be difficult to heal and often prone to infection. That’s why every year, of the 29 million Americans with diabetes, more than 70,000 adults require some type of lower limb amputation.
Unfortunately, what many diabetics don’t know is that the prescriptions they take to help regulate their blood sugar levels can also significantly increase their amputation risk. One of those medications is the billion-dollar blockbuster drug from Johnson & Johnson named Invokana.
Invokana has been at the center of a controversy originating from patients claiming the diabetes medication has caused serious and unexpected side effects such as bone fractures, kidney injuries, diabetic ketoacidosis, and lower limb amputations.
Invokana is manufactured by Janssen Pharmaceuticals, a division of Johnson & Johnson, for the treatment of type 2 diabetes. Also known by its generic name canagliflozin, Invokana was the first in a class of drugs called sodium glucose co-transporter 2 (SGLT2) inhibitors, and was initially developed1 by pharmaceutical company Mitsubishi Tanabe Pharma Corporation (previously known as Tanabe Seiyaku Ltd.) before it was licensed out to Janssen for further development and worldwide marketing.
After undergoing clinical testing and proving its efficacy, the U.S. Food and Drug Administration approved a new drug application for Invokana in March, 2013. Authorization for the drug was also granted by the European Medicines Agency shortly after. At the time of approval, Janssen Pharmaceuticals issued a press release2 hailing Invokana as an important new treatment option for individuals with diabetes.
One of the lead officers at Janssen said that in trials the drug showed blood glucose levels lower or as low as existing diabetes drugs. It was also noted that Invokana was “generally well tolerated” with only mild to moderate side effects.
Invokana Becomes Blockbuster Diabetes Drug
Since 2013, the use of Invokana and other SGLT2 inhibitors has grown exponentially. Sales3 for Invokana were $586 million in 2014 and $1.3 billion in 2015. These massive numbers for Invokana came despite FDA approval of two competing SGLT2 inhibitors called Jardiance and Farxiga in 2014.
Janssen also received approval for two additional versions of canagliflozin.The FDA approved Invokamet in 2014 and its extended release version Invokamet XR in 2016.
Millions of people have been prescribed Invokana and other SGLT2 inhibitors since they were first approved. While sales have slipped4 the past few years over concerns of side effects, Invokana still brings in hundreds of millions of dollars annually for Johnson & Johnson.
How Invokana Works
Invokana is a once-daily oral medication approved to treat type 2 diabetes in adults.
In type 2 diabetes, the body develops a resistance to insulin and is unable to keep blood glucose levels within normal ranges. Invokana helps lower blood glucose levels by inhibiting a carrier called sodium glucose co-transporter 2 (SGLT2). SGLT2 is responsible for glucose being reabsorbed into the bloodstream. By inhibiting it, Invokana prevents reabsorption and promotes the loss of glucose in the urine.
Invokana Side Effects
Like all drugs, Invokana is associated with several side effects. The most common side effects5 of the drug are mild. These include:
- Changes in urination
- Urinary tract infection
- Yeast infection
- Skin sensitivity
- Genital itching
- Dry mouth
- High cholesterol
Invokana Amputation Risks & Other Serious Complications
In the years since Invokana was first approved, more severe complications and risks have come to light. Here is a breakdown of some of the serious side effects.
Lower Limb Amputations
People with diabetes already have a higher risk of amputation in lower limbs, but two large clinical trials6 confirmed that patients taking Invokana were roughly twice as likely to suffer amputations compared to those taking a placebo. Amputations of the toe and middle of the foot were most common, but many also suffered leg amputations. Some even had to undergo amputations of both legs.
The findings culminated in a black box warning — the strongest issued by the FDA — on the labels of all drugs containing canagliflozin in May, 2017.
SGLT2 inhibitors have also been linked to a potentially life-threatening condition called diabetic ketoacidosis. The complication is typically associated with type 1 diabetes and occurs when there are high levels of ketones in the blood from a breakdown of fatty acids. When ketones build up in the body, they can become toxic.
In May, 2015, the FDA issued a safety communication7 warning that Invokana and other SGLT2 inhibitors could lead to ketoacidosis. The agency received 20 confirmed cases of ketoacidosis in patients taking the class of drugs between March, 2013 and June, 2014. All patients required visits to the emergency room or hospitalization. Since then, the FDA has received more reports of ketoacidosis.
Ketoacidosis warnings were added to labels in December, 2015.
SGLT2 inhibitors may also raise the risk of acute kidney injury. The FDA received 73 confirmable cases of acute kidney injury caused by Invokana between March, 2013 and October, 2015, though the numbers may be higher. In about half of the cases, the injury started within a month of taking the drugs and stopped progressing shortly after treatment ended.
Kidney injuries can be serious and irreversible, and the FDA strengthened8 existing warnings on canagliflozin and dapagliflozin drug labels in June, 2016.
Some of the most common side effects are urinary tract infections and yeast infections in both men and women. While these infections are typically manageable, patients taking SGLT2 inhibitors are more likely to develop recurring infections.
In some cases, serious urinary tract infections can lead to a life-threatening blood infection called urosepsis or kidney infection called pyelonephritis. Dozens of patients required hospitalization to treat kidney failure stemming from a urinary tract infection. The FDA added warnings9 to labels in, 2015.
Hundreds File Invokana Lawsuits
Countless patients around the country have been hospitalized or died from serious side effects that were not initially reported on Invokana warning labels. Because Janssen has a responsibility to warn consumers of potentially life-threatening risks, victims have taken to the legal system in pursuit of compensation and justice.
Some of the most common claims levied against Janssen and Johnson & Johnson include a failure to warn of risks, manufacturing a defective drug, downplaying risks, deceptive advertising, failure to test drugs adequately, and more.
The types of injuries people are suing for vary from diabetic ketoacidosis to lower limb amputations.
Invokana Lawsuits Headed to Trial
More than a thousand cases have been filed in federal and state courts around the country. As litigation advanced, consolidation occurred. In late 2017, nearly a thousand cases were centralized in a New Jersey federal court by the U.S. Judicial Panel on Multidistrict Litigation.
Several bellwether trials in the Invokana federal litigation have already been set, and these outcomes will give both sides some idea on how the remaining cases may be decided. The information is then used to determine whether a settlement could be reached between the two sides.
The first bellwether trials are expected to begin in September, 2018.