The Ministry of Food and Drug Safety (MFDS) announced changes in approving SGLT2 inhibitors on Tuesday.

The changes reflected a review of safety information by Health Canada (HC) and the U.S. Food and Drug Administration (FDA). They affect 734 products from 47 companies, containing dapagliflozin, empagliflozin, and ertugliflozin.

Representative products include AstraZeneca Korea's Sidapvia (dapagliflozin and sitagliptin), HK inno.N's Dapa-N (dapagliflozin propanediol hydrate), Bayer Ingelheim's Jardiance (empagliflozin), and MSD Korea's Steglatro (ertugliflozin L-pyroglutamic acid).

The main change is the strengthening of ketoacidosis warnings. Specifically, post-marketing reports have been added that diabetes and ketoacidosis may persist for up to two weeks after discontinuation of SGLT2 inhibitors. While glucose excretion was generally recognized to persist for three days after discontinuation, symptoms have been observed to persist for up to six days in some patients.

In addition, “ketogenic diet” was added as a new risk factor for ketoacidosis, and “type 2 diabetes” was added as an example of a pancreatic disorder that causes insulin deficiency. Previously listed risk factors included reduced insulin dose, acute febrile illness, calorie restriction due to surgery, and alcohol abuse.

The ministry will accept comments on the proposed changes until March 6. Pharmaceutical companies should submit their comments with supporting data for review.