Canagliflozin, a drug that is sold under brand names Invokamet and Invokana, has been known to cause ketoacidosis, kidney damage and heart attacks. Now, the US Food and Drug Administration (FDA) has released a further warning, stating that it also increases the risk of losing bone density, a condition known as osteoporosis.
“The U.S. Food and Drug Administration (FDA) has strengthened the warning for the type 2 diabetes medicine canagliflozin (Invokana, Invokamet) related to the increased risk of bone fractures and added new information about decreased bone mineral density. Bone mineral density relates to the strength of a person’s bones. To address these safety concerns, we added a new Warning and Precaution and revised the Adverse Reactions section of the Invokana and Invokamet drug labels.”
Clinical studies have demonstrated that elderly people who have type 2 diabetes and who were treated with canagliflozin for a period of two years or longer had higher levels of reduced bone density, particularly in their hips and lower spines. Consideration was given to the fact that elderly people already lose bone density. What the clinical trials showed was that those who were treated with Invokana saw a rapid acceleration in this bone loss process. In fact, there were patients who had only been treated with the drug for three months who would already suffer bone fractures. The highest risk for both fractures and bone loss was experienced by post menopausal women.
The research took two years to complete and it was part of a post marketing safety evaluation. Some 700 geriatric patients took part in the study. On September 10, 2015, the FDA released an official statement about the results of the study.
“The additional data confirm the finding that fractures occur more frequently with canagliflozin than placebo. 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.”
The additional data that is referred to in this statement relates to the nine other clinical trials that have been conducted so far. In these, test subjects were prescribed canagliflozin for a period of around 85 weeks.
Because this new data has been released, all Invokana and Invokamet prescribing information will have to have stronger warnings added to them. The advice of the FDA is that prescribing physicians also carefully weigh up the possible risk of bone fractures before they prescribe it to their patients as a diabetes treatment.
Invokana is not the only drug of its kind that is being monitored either. It is classed as an SLGT2 inhibitor, or a gliflozin. Gliflozins are prescription drugs that are designed to target a very specific protein, in this case, sodium glucose co-transporter 2 (SLGT2). This is a protein that helps the kidneys reabsorb glucose (blood sugar). Before it was noted that there is an increased chance of osteoporosis, it had already been found that SGLT2 inhibitors have quite serious side effects.
“In May 2015, the FDA warned that Invokana may lead to a serious condition called diabetic ketoacidosis (DKA). DKA occurs when the body cannot use sugar (glucose) as a fuel source because there is either too little or no insulin. Instead, the body breaks down fat for energy. The breakdown of fat produces ketones which can build up in the body. When these waste products build up in the blood, they become toxic.”
In fact, between March 2013 and June 6, 2014, the FDA received 20 individual reports of patients who had ketoacidosis and who were treated with SLGT2 inhibitors. All 20 of these patients required immediate hospital treatment to help save their lives. While this led to the FDA changing the warning label on the drug and its prescribing information, the agency continues to receive reports of patients who develop ketoacidosis as a result of taking the drug.
Besides osteopororsis and kidney damage, there is also an increased risk of developing urinary tract infections, hypoglycemia (dangerously low blood sugar levels) and vaginal yeast infections. This is true for all SLGT2 inhibitor drugs, including Glyxambia (linagliptin), Jardiance (empagliflozin) and Farxiga (dapagliflozin). As a result, the FDA has placed all these drugs under scrutiny to protect the general public.
The FDA has also requested that physicians monitor any patients to whom they prescribed the drug for diabetic ketoacidosis. The journal Diabetes Care recently published a report that noted the increased risk of developing diabetic ketoacidosis in patients who were prescribed gliflozin drugs.
“Serious adverse events of DKA and related events were reported in 12 patients (0.07%), including 4 (0.07%), 6 (0.11%), and 2 (0.03%) treated with canagliflozin 100 and 300 mg and comparator, respectively; corresponding incidence rates were 0.522, 0.763, and 0.238 per 1,000 patient-years, respectively. Most patients with DKA and related events had a blood glucose > 300 mg/dL (16.7 mmol/L) at presentation of DKA, were on insulin, and had DKA-precipitating factors, including some with type 1 diabetes/latent autoimmune diabetes of adulthood.”
Those found to suffer serious diabetic ketoacidosis as a result of taking the medication were all taken for hospital treatment. Had the condition not been properly treated, patients would have lapsed into a coma. These comas can often prove to be fatal.
It is important to understand how this information relates to the approval process of the FDA. This is something that the Diabetes Journal also pointed out.
“It is not unusual that serious safety issues related to a new drug go undetected during the relatively short clinical development programs for regulatory drug approval.”
Invokana was first introduced to the market as an innovative and revolutionary drug. It didn’t take long, however, for complaints to arise. Furthermore, there are no suggestions that both Janssen, the manufacturer of the drug, and the FDA itself knew that the dangers were present yet still decided to approve and market the drug.
Very often, when a new ‘miracle’ drug is released, they are rushed out to the market before sufficient testing has been completed. While there are plenty of medical experts who said that canagliflozin was unsafe, the FDA still approved it to the market as whole. They simply stated that they would use their own tools and techniques in order to address any adverse effects.
Within the world of medication, however, profits are king. It is believed that by 2017, the market for drugs that cover diabetes will exceed $55 billion. Because of this, Janssen is not overly encouraged to perform unbiased, rigorous tests on their products. However, even Janssen is starting to suffer from the effects of various liability cases.