Invokana (canagliflozin) belongs to the SGLT2 inhibitor class of diabetes drugs along with Invokamet, Farxiga, Xigduo, Jardiance, and Glyxambi. They force the kidneys to excrete more sugar in urine to lower blood-sugar levels.
The researchers looked at 50,220 patients with type-2 diabetes who started taking an SGLT2 inhibitor and compared rates of ketoacidosis with 90,132 patients who started a DPP-4 inhibitor like Januvia (sitagliptin). DPP-4 inhibitors force the pancreas to make more insulin.
Patients on SGLT2 inhibitors were twice as likely to develop diabetic ketoacidosis (DKA), a life-threatening condition that occurs when the blood becomes too acidic.
Study author Dr. Michael Fralick admitted the risk “sounds frightening,” but he estimated only 5 to 8 cases of ketoacidosis per 1,000 patients who start an SGLT2 inhibitor. Even so, he recommended vigilance:
This is something that can happen relatively quickly, so that’s why I think it’s important right after patients are started on these drugs that they’re closely monitored and the clinician considers ordering bloodwork.”
The FDA has issued several Safety Alerts about ketoacidosis from Invokana and other SGLT2 inhibitors, with 73 cases reported from March 2013 to May 2015. All patients required hospitalization or treatment in an emergency department.
In many cases, diagnosis and treatment were delayed because patients on SLGT2 inhibitors with ketoacidosis had blood-sugar levels that were relatively normal. The cases were unusual because ketoacidosis is mostly seen in type-1 diabetics with very high blood-sugar.
The FDA recommends that patients stop taking their SGLT2 inhibitor and seek medical attention immediately if they have any symptoms of ketoacidosis, such as nausea, vomiting, abdominal pain, tiredness, and trouble breathing.