SGLT2 Drugs Increased Risk Of Diabetic Ketoacidosis. Researchers from Brigham and Women’s Hospital in Boston say a new class of type diabetes drugs is associated with an increased risk of diabetic ketoacidosis, a serious complication.
In 2015, the U.S. Food and Drug Administration (FDA) issued a warning about the ketoacidosis risk. The objective of the new study—published on June 8, 2017 in the New Journal of Medicine—”was to assess the risk of diabetic ketoacidosis after the initiation of an SGLT2 inhibitor.”
The researchers used the Truven MarketScan, a large claims database of commercially insured patients in the United States, to identify patients 18 year and older who had newly started treatment with either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor between April 1, 2013 and December 31, 2014 (before the FDA warning).
SGLT2 inhibitors include Invokana, Jardiance, and Farxiga. DPP4 inhibitors include Januvia, Onglyza, and Tradjenta.
DPP4 inhibitors were chosen for comparison because they are also used as second-line treatment for diabetes but have no known association with diabetic ketoacidosis. The researchers excluded patients with human immunodeficiency virus (HIV) infection, end-stage kidney disease, cancer, type 1 diabetes, or past diabetic ketoacidosis. They looked for hospitalization for diabetic ketoacidosis (using the primary position code of the International Classification of Diseases, Ninth Revision) within 180 days after the patient began taking an SGLT2 inhibitor or a DPP4 inhibitor.
Diabetic ketoacidosis is a serious condition in which toxic acid builds up in the bloodstream. Ketoacidosis is caused by excess ketones, acidic compounds that are produced when fat is metabolized. When cells cannot get enough glucose to meet their energy needs, they start using fat for energy instead. Cells that are starved for glucose produce an abundance of ketones.
Diabetic ketoacidosis can be life threatening. Without prompt and appropriate treatment, diabetic ketoacidosis can result in
- cerebral edema (swelling of the brain)
- acute kidney failure
- respiratory distress
- heart attack
Left untreated, ketoacidosis can be fatal, the researchers said.
Parker Waichman LLP has represented individuals in scores of drug-injury cases, including those involving serious side effects of diabetes drugs. They can answer questions about a possible diabetic ketoacidosis lawsuit.
Comparison of Ketoacidosis Risks
The Brigham and Women’s researchers identified 50,220 patients who had received a new prescription for an SGLT2 inhibitor and 90,132 who had received a new prescription for a DPP4 inhibitor. Patients who were receiving SGLT2 inhibitors were younger and had fewer coexisting illnesses than those receiving DPP4 inhibitors but were more likely to receive insulin. After propensity-score matching was performed, these differences were well balanced. Before propensity-score matching, the unadjusted rate of diabetic ketoacidosis within 180 days after the initiation of an SGLT2 inhibitor was about twice the rate after the initiation of a DPP4 inhibitor (4.9 events per 1000 person-years vs. 2.3 events per 1000 person-years) (hazard ratio, 2.1; 95% confidence interval [CI], 1.5 to 2.9). After propensity-score matching, the hazard ratio was 2.2 (95% CI, 1.4 to 3.6).
Based on their analysis the researchers concluded that patients had approximately twice the risk of diabetic ketoacidosis shortly after starting to take Invokana or other SGLT2 inhibitor compared to starting a DPP4 inhibitor. Diabetic ketoacidosis leading to hospitalization is infrequent, the researchers say. But the increased risk diabetic ketoacidosis with SGLT2 inhibitors “is among the factors to be considered at the time of prescribing and throughout therapy if patients present with symptoms suggestive of diabetic ketoacidosis.”
SGLT2 inhibitors are a new class of prescription medicines approved by the U.S. Food and Drug Administration (FDA) to lower blood sugar in adults with type 2 diabetes. SGLT2 inhibitors cause the kidneys to remove sugar from the body through urination. Medicines in the SGLT2 inhibitor class include canagliflozin (Invokana, Invokamet), dapagliflozin (Farxiga), and empagliflozin (Jardiance, Glyxambi).
Invokana, which received FDA approval in 2014, was the first SGLT2 inhibitor to come to market. But by 2015 the FDA issued a warning about the increased risk for diabetic ketoacidosis when SGLT2 inhibitors are used.
In addition to diabetic ketoacidosis, Invokana is linked to reports of heart attacks, bone fractures, kidney damage and kidney failure. SGLT2 inhibitors have been linked to increased risk for urinary tract infections (UTIs), which can progress into severe kidney and blood infections.
Patients who have experienced the SGLT2 side effects have filed lawsuits alleging that the makers of Invokana and other SGLT2 inhibitor drugs knew about the ketoacidosis risk but concealed the information to avoid harming sales of their drugs. One hundred twenty-six cases have been consolidated in a multidistrict litigation (MDL), before U.S. District Judge Brian R. Martinotti in the District of New Jersey.