The US Food & Drug Administration has warned patients and physicians that some of the country's most popular type 2 diabetes drugs can, in rare cases, cause a flesh-eating bacterial infection of the genitals. Learn more about an Invokana lawsuit commercial.
On August 29, 2018, the FDA drew a link between the class of SGLT2 inhibitors, diabetes drugs that stimulate urine output, and necrotizing fasciitis of the perineum, or Fournier's gangrene. Fournier's gangrene is also sometimes referred to as genital gangrene.
The condition, which is exceedingly rare, can lead to amputation of the penis and testicles in men. SGLT2 inhibitors are some of the most widely-used diabetes drugs in America.
The class includes Invokana and Invokamet, medications manufactured by Janssen Pharmaceuticals, along with Jardiance and Farxiga. Over recent decades, the drugs have been linked to a host of severe side effects, including kidney disorders and limb amputations.
In a Drug Safety Communication published on Wednesday, August 29, experts at the FDA said their new warning was sparked by a series of adverse event reports. These reports, submitted to the FDA by patients and healthcare providers, described cases of Fournier's gangrene in patients taking SGLT2 inhibitors.
FDA reviewers say they have identified 12 cases of the condition in SGLT2 inhibitor patients, through a search of the FDA's adverse event reporting system and the medical literature. "All 12 patients were hospitalized and required surgery," the FDA wrote in its release. "Some patients required multiple disfiguring surgeries, some developed complications, and one patient died."
Fournier's gangrene is a form of necrotizing fasciitis, or flesh-eating bacteria. The bacteria enter the body, usually through a cut or break in the skin, "where they quickly spread and destroy the tissue they infect," the FDA writes. In Fournier's gangrene, the flesh-eating bacteria attacks the tissue "under the skin that surrounds muscles, nerves, fat, and blood vessels of the perineum," the area between the anus and the scrotum or vulva.
While Fournier's gangrene is most often seen in men, the FDA says that cases involving SGLT2 inhibitors are split between the sexes. Of the 12 cases identified from the medical literature, 5 of whom were women.
Diabetic patients already live at an increased risk for Fournier's gangrene. Other risk factors for necrotizing fasciitis include cancer, obesity, alcoholism, peripheral vascular disease and other conditions that compromise immune system function. In most cases, the bacterial infection is not spread between people.
The condition is exceedingly rare. Citing research, the FDA estimates that the condition occurs in 1.6 out of 100,000 American males every year, usually striking in men between the ages of 50 and 79.
Given these statistics, 12 reports of Fournier's gangrene, found within a 5 year time span (the FDA's review only covered the years between March 2013 and May 2018), is high. In contrast, the FDA notes, only 6 cases of Fournier's gangrene could be found in patients taking other anti-diabetic drugs over a span of more than 30 years. As a result, FDA reviewers believe that SGLT2 inhibitors, including Invokana, could increase the risk for this rare, but life-threatening, form of infection.
SGLT2 inhibitors were introduced to the world diabetes market in 2013. The drugs feature a different mechanism of action than prior diabetes drugs. In an attempt to control blood glucose levels, SGLT2 inhibitors stimulate the excretion of sugar in the urine.
In a Forbes article, Bruce Y. Lee explains how this mechanism of action could increase the risk for Fournier's gangrene. "It's all about making your genitals sweeter," Lee writes, "in a literal and not a figurative sense." As Lee explains, SGLT2 inhibitors work by increasing the sugar output in our urine. Sugar, of course, is the main food source for bacteria. So as the sugar level around our genitals rises, the organs become a more and more attractive breeding ground for microbes.
Researchers have long understood this effect in principle. In fact, yeast and urinary tract infections are already known risks of taking SGLT2 inhibitors. "In rare situations," Lee continues, "bacteria such as Clostridium perfringens, Group A streptococcus, Staphylococcus aureus, and Vibrio vulnificus can cause Fournier's gangrene when they invade" and start destroying genital tissue.
Fournier's gangrene, then, is just a life-threatening extension of risks that SGLT2 inhibitors have presented all along. In fact, urinary tract infection is one of the leading causes of Fournier's gangrene, along with physical trauma, kidney stones and abscesses. Fournier's gangrene can also develop as a surgical complication.
Tragically, at least one SGLT2 inhibitor-related death has been reported as a result of Fournier's gangrene. Beyond the potential loss of a patient's genitals, the condition can turn fatal if the bacteria are allowed to spread.
SGLT2 inhibitor patients have been advised to watch for potential symptoms of Fournier's gangrene, including:
Other symptoms of flesh-eating bacteria include severe pain and induration, a hardening of the skin and soft tissues. The skin may begin red, but then turn purple or black as the blood clots within the dying flesh. As the nerves below the skin die, patients may lose sensation in the affected tissue. Patients who experience these symptoms should seek treatment immediately.
Doctors have been warned to assess patients for Fournier's gangrene if they present with the symptoms listed above. In cases where Fournier's gangrene is suspected, patients should be started on antibiotics immediately. Flesh-eating bacteria can spread extremely rapidly, so patients require attention as soon as possible.
Some patients may require surgical debridement; sections of dead flesh may have to be surgically removed to prevent the bacterial infection from spreading. Surgery is almost always required in cases of necrotizing fasciitis, or flesh-eating bacteria, because the bacteria have burrowed deep below the skin. In severe cases, the genitals may be amputated.
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