A recently published study suggests that diabetic ketoacidosis associated with Invokana and other SGLT2 inhibitor Type 2 diabetes drugs, while often severe, is preventable, provided that doctors and patients are able to quickly recognize the signs and symptoms of this potentially deadly disorder.
Diabetic ketoacidosis, also known as ketosis or ketoacidosis, is a dangerous disorder that occurs when toxic blood acids called ketones accumulate in the blood. While Type 1 diabetics are most likely to develop the condition, a growing number of reports have suggested that the use of SGLT2 inhibitors may increase the risk for ketoacidosis in Type 2 diabetics.
Signs and symptom diabetic ketoacidosis include:
If not recognized and treated quickly, ketosis can result in diabetic coma, and even death.
SGLT2 inhibitors are a relatively new class of Type 2 diabetes medication that work by inhibiting the ability of the kidneys to absorb glucose, thereby allowing its elimination from the body via urine.
Invokana, which came to market in 2013, was the first SGLT2 inhibitor approved by the U.S. Food & Drug Administration (FDA). Other drugs in this class include:
In December 2015, the FDA ordered the makers of Invokana and other SGLT2 inhibitors to add new warnings to their product labels regarding a potential risk of diabetic ketoacidosis. The mandate followed a review of the agency’s adverse event database, which uncovered 73 reports of ketoacidosis that had occurred among individuals treated with SGLT2 inhibitors. The FDA advised patients to stop taking their medication and seek medical attention immediately if they develop any symptoms of the disorder.
This latest study, which was published online February 13th in Diabetes Care, involved two separate analysis, the first of which consisted of a South Australia audit of 13 SGLT2 inhibitor-associated ketoacidosis cases reported between December 2015 and April 2017. Eight of these events occurred in adults with Type 2 diabetes, four of whom were also taking insulin. The remaining five involved Type 1 diabetics.
Nine of the patients required intensive/high-dependency care, and all required intravenous insulin and dextrose. One of the patients died due to Takotsubo cardiomyopathy.
In two cases, treating physicians had failed to diagnose diabetic ketoacidosis. In six, doctors were unaware of the link between ketoacidosis and SGLT2 inhibitors.
The second analysis revealed that 82 reports of SGLT2 inhibitor-associated ketoacidosis had been logged with the Australian Therapeutic Goods Administration (TGA) from the time the drugs came to market through April 2017, representing an event rate of about 1.8 cases per 1000 patient-years.
The reported events were usually serious, requiring intensive care in 18 cases and classified as life-threatening in 16 cases.
The authors concluded that because many patients and physicians are unfamiliar with the signs and symptoms of SGLT2 inhibitor-associated ketosis, the condition, though rare, often progresses to a severe stage. However, “identifiable precipitants were often present, suggesting the potential for risk mitigation.”
Hundreds of lawsuits have been filed in U.S. courts on behalf of individuals who suffered ketoacidosis, kidney injuries and other side effects allegedly related to treatment with SGLT2 inhibitors.
Nearly 1,000 federally-filed lawsuits involving Invokana and Invokamet are currently undergoing centralized pretrial proceedings in a multidistrict litigation now underway in in the U.S. District Court, District of New Jersey. An additional 51 claims filed against the manufacturers of Farxiga have been consolidated in the U.S. District Court, Southern District of New York.