Product News and Recalls

SGLT2 Inhibitors and Ketoacidosis: What Patients Should Know

FDA safety announcement issued over ketoacidosis link to SGLT2 inhibitorsLast month, the U.S. Food and Drug Administration (FDA) issued a safety announcement in which it warned of a possible connection between a new type of diabetes medication, called sodium-glucose cotransporter-2 (SGLT2) inhibitors, and ketoacidosis, a serious blood condition wherein the body produces too many blood acids, or ketones. Since the alert, there have been questions from patients as well as practitioners about the drugs’ link to ketoacidosis and the difficulty of recognizing whether people taking SGLT2 inhibitors have ketoacidosis.

The FDA’s mid-May announcement followed a report published earlier that month by the Institute of Safe Medication Practices (ISMP). The report investigated a particular SGLT2 inhibitor called canagliflozen, manufactured and marketed by Janssen Pharmaceuticals as Invokana. ISMP researchers identified 457 adverse event reports in the FDA’s database filed during the Invokana’s first year on the market (2013–14). According to the ISMP, the reports included five different kidney-related adverse effects: kidney failure or impairment; dehydration and fluid imbalances; kidney stones; urinary tract infections; and abnormal or other weight loss.

The ISMP report goes on to question the benefits of Invokana and other SGLT2 inhibitors, and whether these outweigh the risks posed by the drugs. The report notes that at the time it was approved by the FDA, Invokana “had not been tested in a sufficient number of patients for a long enough period of time to answer that question. In the face of that uncertainty about benefit was increasing evidence that canagliflozin is associated with adverse effects in appropriate clinical use” (the most common of which is urogenital infections).

The increased rate of kidney failure in patients taking Invokana is likely a result of how SGLT2 inhibitors work. Most diabetes medications work either by suppressing the production of glucose or by increasing insulin or otherwise facilitating the metabolization of glucose. SGLT2 inhibitors, on the other hand, reduce blood glucose levels by preventing glucose reabsorption in the kidney, where it leaves the body through urine. Too much or too frequent transport of glucose through the kidney can stress renal capacity and lead to kidney and urogenital conditions.

While the ISMP report did not directly attribute any cases of ketoacidosis to Invokana, the identified adverse events implied various signs of renal toxicity related to ketoacidosis.

The link between SGLT2 inhibitors and ketoacidosis is exacerbated by the fact that the condition can easily be missed in patients. Diabetologist Dr. Anne Peters wrote a commentary on warning about recognition of ketoacidosis in SGLT2 inhibitor patients. Peters notes that oftentimes, patients taking SGLT2 inhibitors are euglycemic—that is, they have normal blood glucose levels. For this reason, doctors may overlook ketoacidosis in diabetic patients because it is usually accompanied by hyperglycemia—excessive blood glucose levels. Peters stresses the need for better recognition of the signs and contexts of diabetic ketoacidosis.

The FDA is still looking into the link between SGLT2 inhibitors and ketoacidosis, as is the Canadian government’s public health department, Canada Health. Symptoms of ketoacidosis include difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. Both the FDA and Canada Health are advising patients using SGLT2 inhibitors to seek immediate medical attention should they notice any of these signs of onset.

Speak with your doctor or physician before making any changes to your treatment plan. If you or a loved one was diagnosed with ketoacidosis after taking an SGLT2 inhibitor, contact the pharmaceutical lawyers at Lopez McHugh today to receive your free legal consultation. You may be entitled to compensation through an SGLT2 inhibitor lawsuit.