Endocrinology Societies: No Greater Risk of DKA With Use of SGLT2s Than in Overall Type 2 Diabetes Population

The FDA issued a warning on the SGLT2 inhibitor class in May 2015, but the review by AACE and ACE found that several of the cases involved patients with type 1 disease.

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) have published a joint statement on the safety of SGLT2 inhibitors in patients with type 2 diabetes (T2D), following an FDA warning in May 2015 that the drug class may lead to diabetes ketoacidosis (DKA).

In general, leaders of the AACE and ACE found that the DKA does not occur any more frequently among the T2D population treated with these new drugs than it does generally—and it is uncommon—and the benefits of SGLT2 inhibitors outweigh the risks.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic therapy that work by blocking glucose reabsorption through the endocrine system, causing the person with diabetes to expel excess sugar through the urine. This unique mechanism of action allows the drugs to work well in combination with other therapies, and 1 drug in the class, empagliflozin, has been shown to have a cardioprotective benefit.

Representatives from AACE and ACE convened in October 2015 to discuss the FDA warning, and the result of their discussions were published online April 15, 2016, in Endocrine Practice.

The authors, who include Yehuda Handelsman, MD, FACP, FNLA, FACE; Robert R. Henry, MD, FACE; and Zachary T. Bloomgarden, MD, MACE; concluded: “The incidence of DKA in T2D treated with SGLT2 inhibitors does not appear to exceed the low levels occurring in the general diabetes population. Further study of the mechanisms behind the metabolic effects of SGLT2 inhibitors is needed to better define the risk of DKA with these agents.”

DKA cases that have been reported have involved patients with type 1 diabetes (T1D) involved in clinical trials, or patients with atypical disease who need multiple doses of insulin a day, similar to that of T1D patient. Details in the report suggest that a marker of SGLT2 inhibitor related DKA is insulin deficiency, or events that are known triggers of DKA, such as surgery, extensive exercise, prolonged fasting, or severe infections.

Benefits of SGTL2 inhibitors have included reduced blood pressure and some weight loss, according to recent studies.


Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT2 inhibitors on diabetic ketoacidosis [published online April 15, 2016]. Endocr Pract. 2016; doi: 10.4158/EP161292.PS