US FDA strengthens warning for type 2 diabetes med canagliflozin

Warning related to increased risk of bone fractures, decreased bone mineral density

The US Food and Drug Administration (FDA) has strengthened the warning for the type 2 diabetes medicine canagliflozin (Invokana, Invokamet, Johnson & Johnson/Janssen) 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, the US regulator added a new Warning and Precaution and revised the Adverse Reactions section of the Invokana and Invokamet drug labels.

Healthcare professionals should consider factors that contribute to fracture risk prior to starting patients on canagliflozin. Patients should talk to their healthcare professionals about factors that may increase their risk for bone fracture. Patients should not stop or change their diabetes medicines without first talking to their healthcare professional.

Canagliflozin is a prescription medicine used with diet and exercise to lower blood sugar in adults with type 2 diabetes. It belongs to a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors. Untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. Canagliflozin lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. It is available as a single-ingredient product under the brand name Invokana and also in combination with the diabetes medicine metformin under the brand name Invokamet.

Information about the risk of bone fractures was already in the Adverse Reactions section of the drug label at the time of canagliflozin’s approval. Based on updated information about bone fractures from several clinical trials, the US FDA revised the drug label and added a new Warning and Precaution. The additional data confirm the finding that fractures occur more frequently with canagliflozin than placebo, which is an inactive treatment. 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.

In addition, the US regulator has added new information about the risk of decreased bone mineral density to the canagliflozin label. An FDA-mandated post-marketing safety trial of canagliflozin conducted to evaluate changes to bone mineral density over two years in 714 elderly individuals showed that canagliflozin caused greater loss of bone mineral density at the hip and lower spine than a placebo. This new safety information has been added to the Adverse Reactions section of the drug label.