When a diabetic gets a small cut, it’s a serious concern. For diabetics, a simple blister, cut, crack or sore can become a dangerous ulcer that could lead to a life-changing amputation.
In the past 20 years, the rate of lower limb amputations caused by diabetes complications has decreased by 50 percent. But most diabetics don’t know that the popular diabetes medication Invokana (canagliflozin) can actually worsen their risk.
When the diabetes drug Invokana first hit the market in 2013, it was heralded as a breakthrough for patients who wanted to lower their blood sugar and possibly lose some weight, too. But now, many of those hopeful patients are also wondering why does Invokana cause amputations.
How common are diabetes amputations?
The Centers for Disease Control and Prevention (CDC) estimates 23.6 million Americans currently have diabetes. In the past decade, the number of Americans with diabetes has increased heavily from 18.2 million in 2003.
Amputations are a serious concern for people with diabetes. Most amputations are performed on the lower extremities, primarily of the toes and feet. Though it’s less common, some diabetics require amputations below the knee.
Nearly 67 percent of U.S. amputations are linked to diabetes and related complications. According to the CDC, about 73,000 non-traumatic lower-limb amputations were performed in adults aged 20 years or older with diagnosed diabetes in 2010.
An amputation is the surgical removal of a limb or other body part to extract diseased or dead tissue. Depending on the severity and location, an amputation can severely alter personal identity and limit the ability to participate in daily activities. There’s no doubt that people who experience amputations deal with a lot of pain and suffering.
The amputation rate for people with diabetes is 28 times higher than for people without diabetes. Amputations are more common for men than women, with a 50 percent higher amputation rate for male diabetics. The elderly and the non-Hispanic black population are also affected more frequently.
Why do diabetics have a higher risk of amputation?
There are multiple factors that play a role in amputation. Though many of the issues that create cause for an amputation are related to foot care, some are related to glucose management and unknown medication risks.
Nerve damage and poor circulation, worsened by uncontrolled blood sugar, are two major issues that contribute to the need for an amputation. These complications allow infections to set in without a diabetic’s knowledge, causing a gangrenous wound that could later require an amputation.
About Invokana and Amputations
Certain medications, such as Invokana, can also increase the risk of amputation. Invokana, the trade name for the drug canagliflozin, is prescribed to patients for the treatment of type 2 diabetes. The drug is licensed from Mitsubishi Tanabe Pharma Corporation to Johnson & Johnson’s Janssen Pharmaceuticals division for distribution throughout most of the world.
According to Janssen Pharmaceuticals, Invokana lowers blood sugar (A1C) and the 300-mg dose is proven to reduce A1C levels more effectively than a competing drug from Merck called Januvia.
What is the reason for the FDA Invokana amputation warning?
Known Invokana side effects include ketoacidosis, kidney problems, urinary tract infections and a higher risk of broken bones. Amputation risk, however, is a new concern for users of the popular diabetes medication.
In 2017, the U.S. Food and Drug Administration began requiring new ‘black box’ warnings to be added to Invokana labels to describe the increased risk of leg and foot amputations to patients.
The FDA acted following two large clinical trials, CANVAS and CANVAS-R, in which the data demonstrated that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with a placebo.
What did the Invokana amputation study show?
During the clinical trials, the researchers found that patients most often experienced amputations of the toe and middle of the foot. But, other patients had amputations involving the leg, below and above the knee. In addition, some had more than one amputation and some had both limbs amputated.
One of every 69 patients who take Invokana for five years will have a drug-related amputation.
Despite the increased risk, the trials did not answer the question of why does Invokana cause amputations. According to an article in Forbes, some doctors speculate that while the drug decreases blood sugar and blood pressure, it may also cause the blood to thicken and subsequently pool in the foot.
As researchers struggle to explain why the amputations occur, the FDA did make a note of which types of patients might be predisposed to amputation if they decide to take Invokana. The factors that appeared to increase the odds of amputation included a prior history of amputation, peripheral vascular disease, neuropathy and diabetic foot ulcers.
How to Prevent Diabetic Amputations
What are the risk factors for diabetic amputations?
Diabetics have sensitive feet that are more vulnerable to injuries, especially when blood glucose in unmanaged. All of the factors that lead to amputations actually work together, so it’s important to be aware of each one.
Diabetic neuropathy reduces sensation, making patients unaware they have injuries because they can’t feel wounds developing. Poor circulation, on the other hand, keeps injuries from healing properly. Knowing the risk factors for diabetic amputation are key to prevention.
Diabetic neuropathy, a common diabetes complication, is a form of nerve damage caused by high blood sugar. It injures nerve fibers throughout the body, leaving patients with decreased feelings in the lower limbs and feet. Because of neuropathy, diabetics may not feel hot or cold temperatures. They might not notice a cut or callous that makes them more vulnerable to infection.
“You could have a tack or stone in your shoe and walk on it all day without knowing. You could get a blister and not feel it. You might not notice a foot injury until the skin breaks down and becomes infected.”
– American Diabetes Association
There are four types of diabetic neuropathy: peripheral neuropathy, autonomic neuropathy, radiculoplexus neuropathy and mononeuropathy. Symptoms of diabetic neuropathy might include pain, numbness, tingling, burning. For some people with neuropathy, digestive issues, bladder problems, vision complications, erectile dysfunction are experienced.
Diabetes may affect blood vessels, causing them to narrow, harden. This limits blood flow to the legs and feet. A lack of blood flow can affect the ability to fight infections in addition to slowing the speed of wound healing. Some identifiable indicators of poor circulation include peripheral vascular and arterial disease.
Smoking also affects the small blood vessels in the body. Smoking can reduce blood flow throughout the limbs, and it makes injuries harder to heal. Many diabetes who require amputations are smokers.
Skin Changes, Calluses, Ulcers
Skin changes, related to nerve damage, affects the natural oils and moisture in the feet. When diabetes affects the skin of the feet and toes, it causes dryness. Dryness makes the skin more likely to peel and crack. If the natural regulatory state of the foot changes, it makes the patient more vulnerable to injury, infection and amputation.
Calluses, caused by repeated friction, pressure or irritation, are also more common with diabetes. Untrimmed and untreated calluses can cause complications, which frequently occur on the ball of the foot or on the bottom of the big toe. Calluses may develop into ulcers, which are painful open sores.
Neglecting or walking on ulcers can result in deeply embedded infections. Many of these wounds are non-healing, which may lead to the loss of a limb.
People with diabetes are already at a higher risk of amputation, but studies show the popular medication Invokana can double the risk. The reason for an Invokana amputation is not yet clearly understood. However, researchers confirm that Invokana in conjunction with other risk factors makes amputation more likely.
A history of prior amputation may also predispose patients taking Invokana to the need for amputation. Patients with a history of amputation or peripheral vascular disease had the highest amputation risk, but the relative risk was similar. Regardless of a prior risk, diabetic patients are encouraged to talk to their doctors about the potential amputation side effects of Invokana.
Most diabetic foot infections require some surgical intervention, but many foot problems are actually avoidable. It’s possible to prevent diabetic foot ulcers and amputations by understanding the risk factors, key elements of proper care and any and all medication risks upfront.