SGLT2 inhibitors for diabetes may cause ketoacidosis

The FDA just came out with a warning on the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, including canagliflozin dapagliflozin, and empagliflozin (and the combo drugs including them) because of 20 cases of ketoacidosis. these drugs lead to increased urinary excretion of glucose, thereby lowering hemoglobin A1C. see http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm​ for the press release. findings of FDA:

--from March 2013 to June 2014, there were 20 cases of ketoacidosis reported requiring emergency room visits, an unusual finding in type 2 diabetes. and there have been additional reports since June 2014.
--1/2 the cases did not have any typical DKA triggering factors, such as acute illness (urinary tract infection, urosepsis, gastroenteritis, influenza, trauma), reduced caloric or fluid intake, reduced insulin dose; also no factors associated with high anion-gap acidosis (hypovolemia, acute renal failure, hypoxemia, reduced oral intake, history of alcohol use)
--of note, the glucose levels in the patients were "only mildly elevated at less than 200 mg/dL in some reports, while patients with type 1 diabetes who have DKA typically have glucose levels greater than 250 mg/dL."
--median time to development of DKA was 2 weeks after initiation of drug therapy with SGLT2 inhibitor, but the spread was great (range 1 to 175 days) [and may be much greater as we are more alert to this association and discover more cases]
--the FDA with continue to monitor these drugs to see if there needs to be changes in labeling.

so, as I've mentioned before, I am really reluctant to use these new-fangled drugs. in part because they are new and untested long-term (and this is a case in point). in part because none of them have looked at the important clinical endpoints (death, heart disease, microvascular complications, etc) but only at the effect on the surrogate marker of hemoglobin A1C. and, in part, because of the hassle of getting prior approvals from insurance companies to use these new and expensive meds. the other take-home message for us is to be alert to the possibility of DKA even in patients with blood sugar <200 mg/dL...

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