Invokana May Increase Bone Fracture Risk: FDA

Follows evidence linking the SGLT2 inhibitor to fractures

• by Parker Brown
  Staff Writer, MedPage Today

The FDA strengthened the warning for type 2 diabetes drug canagliflozin (Invokana, Invokamet) to note that the drugs may increase the risk of bone fracture and decrease bone mineral density.
In a drug safety communication, posted today, the agency said they have added a new warning and precaution and have revised the adverse reactions section of the drug labels to reflect this fact.
Last year, a researcher wrote in Lancet Diabetes & Endocrinology that there is a possible relationship between the drug, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and bone fractures, especially for post-menopausal women. She cited numerous studies showing a possible link as evidence.
The FDA said that healthcare professionals should consider factors that may contribute to fracture risk before starting their patients on canagliflozin. They also added the following information:

• Bone fractures have been seen in patients on canagliflozin
• Fractures can occur as early as 12 weeks after starting the drug
• In addition to bone fractures, canagliflozin has also been linked to decreases in bone mineral density at the hip and lumbar spine

The agency said that the warning came after an evaluation of nine pooled clinical trials with an average exposure to the drug of 85 weeks. The incidence rates of bone fractures was 1.1 in the comparator group, 1.4 for those on 100 mg of canagliflozin, and 1.5 for those on 300 mg. The fractures were more likely to be low trauma and affect the upper extremities.
They added that a trial of 714 patients was conducted as a postmarketing requirement to evaluate the safety of the drug. At two years, patients randomized to 100 mg of the drug had placebo-corrected declines of 0.9% in bone mass density of the hip, and those on 300 mg had a 1.2% decline. They also had a 0.3% decline and 0.7% decline, respectively, at the lumbar spine, and declines were also noticed in the femoral neck and the distal forearm.
Other side effects of canagliflozin may include dehydration, kidney problems, low blood sugar (when used with other diabetes medications), high potassium levels in the blood, increased cholesterol, and yeast infections. The FDA asked that healthcare professionals and patients are encouraged to report adverse events related to this drug to their MedWatch Safety Information and Adverse Event Reporting Program.