Sodium-glucose co-transporter 2 (SGLT-2) inhibitor drugs are the newest class of prescription medications to treat Type 2 diabetes. These SGLT-2 inhibitor drugs block the absorption of glucose into the bloodstream. Invokana was the first SGLT-2 drug introduced by manufacturers Janssen Pharmaceuticals and Johnson & Johnson, and is still the best-selling drug in its class. In fact, Invokana is expected to reach “blockbuster” status during 2015, meaning it would reach the $1 billion mark.
Following the introduction of Invokana, AstraZeneca and Bristol Myers Squibb brought Farxiga to the market. Invokana and Farxiga were quickly followed by Jardiance, Invokamet and Xigduo XR in 2014, and, in February 2015, Glyxambi. Unfortunately, within a year of Invokana’s approval, the FDA had received over 450 adverse event reports related to potentially serious, even fatal conditions associated with SGLT-2 inhibitors.
Ketoacidosis—a Potentially Fatal Condition
By May 2015 the FDA was warning the public of the risk of ketoacidosis associated with Invokana and other SGLT-2 inhibitor drugs. Ketoacidosis is a very serious condition which can lead to hospitalization, swelling of the brain, severe dehydration, coma and death. SGLT-2 inhibitors don’t work on insulin production through the metabolism of excess insulin as older diabetic drugs do. Instead, the person’s kidneys are targeted. The SGLT-2 inhibitors increase sugar excretion through urine, preventing the sugars from being reabsorbed into the kidneys.
Ketoacidosis occurs when high levels of blood acids (ketones) build up in the bloodstream after the body has lost its ability to produce sufficient insulin. With insufficient insulin in the body, it begins to use fat as an alternative fuel source, building up toxic levels of ketones. Typically, ketoacidosis occurs only in those with Type 1 diabetes (juvenile diabetes), however doctors are seeing more cases of ketoacidosis among patients taking Invokana or other SGLT-2 inhibitor drugs.
Kidney Failure and Kidney Damage Related to Invokana
Kidney failure and kidney damage have also been related to Invokana. In a clinical trial performed by Invokana manufacturer Janssen Pharmaceuticals, it was noted that there were certain Invokana issues associated with impaired renal function. Invokana was found to increase serum creatinine and decrease eGFR. Janssen’s clinical trial found that renal function abnormalities can occur after patients begin taking Invokana. Frequent monitoring for renal function is essential in all at-risk patients. The elderly are also at a significantly higher risk for developing kidney failure or kidney damage when taking Invokana.
Cardiovascular Events Related to Invokana
While ketoacidosis and kidney damage have been at the forefront of the Invokana debate, there are other, equally serious health issues, linked to Invokana and other SGLT-2 inhibitors. Heart attack and stroke are two such issues. In a January 2013 meeting of the FDA, Janssen Pharmaceuticals gave a number of presentations on the “wonders” of their latest drug, Invokana. A question and answer session was held after the presentations. At that time the co-founder and director of Public Citizen’s Health Research Group, Dr. Sidney Wolfe, raised some thought-provoking questions. Dr. Wolfe’s primary concern was blood clots which could, in turn, lead to heart attacks.
Dr. Wolfe noted in Janssen’s own studies, thirteen people taking Invokana experienced a cardiovascular event. Wolfe stated Invokana heart attack risks could be significant, due to the increase in hematocrit among those taking the drug. Hematocrit is the concentration of red blood cells; normally a woman has 40 percent concentration while a man has 45 percent. Dr. Wolfe believed at least 25 percent of those taking Invokana would eventually have a hematocrit of 47 percent—a “very dangerous range.” Despite these valid concerns, the FDA approved Invokana, only asking that Janssen conduct a post-market study to determine how many patients experienced heart attacks or strokes as a result of taking Invokana.
Was Janssen and J & J Aware of the Health Issues Related to Invokana?
The question as to whether Janssen and J & J were aware of the potentially severe health issues associated with Invokana may eventually become extremely important. If, in fact, the manufacturers were aware of the potential of Invokana to cause ketoacidosis, renal damage, renal failure, heart attack and stroke, then there may have been a blatant failure to warn.