FDA warns on AZ, Lilly and J&J diabetes drug safety

The FDA has warned that patients taking a newer class of diabetes drugs may cause dangerously high level of blood acids, which could require hospitalisation.

The sodium-glucose cotransporter-2 (SGLT2) inhibitor drugs include Johnson & Johnson's (J&J) Invokana (canagliflozin) AstraZeneca's (AZ) Farxiga (dapagliflozin) from J&J and Lilly and Boehringer Ingelheim's (BI) Jardiance (embagliflozin).

The US regulator has issued the warning because of numerous reports of serious cases of the side effect, known as ketoacidosis.

The FDA Adverse Event Reporting System (FAERS) database found 20 cases of acidosis reported as diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients treated with SGLT2 inhibitors from March 2013 to 6 June 2014. All patients required emergency room visits or hospitalisation to treat the ketoacidosis.

The regulator stopped short of making a direct link between the side effects and the drugs, as a number of other clinical issues could have contributed to the problems.

However the risk of ketoacidosis is already known among the class, and the side effect is not usually seen in type 2 diabetes patients. Moreover DKA is normally accompanied by high blood sugar levels, but in these patients blood sugar levels were only slightly elevated.

The FDA says it is continuing to monitor the issue, and may decide that the drugs require stronger warnings in their prescribing information.

This would certainly hit sales of the newer drugs, which have grown rapidly. J&J's Invokana is the market leader, having been the first to market in 2013. The drug earned $278 million in the first quarter of 2015, putting it on course to exceed the $1 billion mark this year, unless the new safety warnings concern doctors and patients. Its competitors are some way behind, but if one drug can demonstrate a superior safety profile – Lilly and BI's Jardiance has been touted as such – then this could be a significant factor in the long term.

The warning also covers combination drugs containing SGLT2 inhibitors, including AZ's Xigduo XR (dapagliflozin/metformin), J&J's Invokamet (canagliflozin/metformin), and Lilly and BI's Glyxambi (empagliflozin/linagliptin).