Euglycemic diabetic ketoacidosis (euDKA) is a rare but life-threatening adverse effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We present a case of delayed euDKA seven days after cure of acute pancreatitis and discharge from the hospital of a 51-year-old man with type 2 diabetes mellitus (T2DM) managed with a combination of antidiabetic medications, including the SGLT2 inhibitor dapagliflozin. Prior acute pancreatitis was postulated to be a contributing factor to the development of SGLT2 inhibitor-associated euDKA in this patient discharged from the hospital. The patient was managed accordingly and improved clinically while his oral hypoglycemic agents were stopped. The risk of euDKA from SGLT2 inhibitor therapy may be increased by some stress factors (eg, infection, surgery, acute illness, low-carbohydrate diet, excessive alcohol intake). As these SGLT2 inhibitors become a popular therapeutic strategy for the management of hyperglycemia in T2DM, clinicians should be aware that acute illnesses such as pancreatitis in patients with T2DM can be potential predisposing factors for the development of SGLT2 inhibitor-associated euDKA.

OBJECTIVE: To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS).
METHODS: Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases.
RESULTS: A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31 days, and canagliflozin had the longest onset time (96.5 days for euDKA and 75 days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA.
CONCLUSIONS: Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.

Diabetic ketoacidosis (DKA), an acute and life-threatening complication of diabetes, is a metabolic disorder caused by insulin deficiency and an increase in counter-regulatory hormones. Several cases of DKA without marked hyperglycemia have been reported and are defined as euglycemic DKA (eu-DKA). The use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) is associated with the occurrence of eu-DKA, of which, dapagliflozin is one of the agents. In this study, we report a case of dapagliflozin-associated eu-DKA following surgery for pancreatic carcinoma. A 57-year-old woman presented with acute abdominal pain after surgery for pancreatic carcinoma. Emergency exploratory laparotomy was performed because of suspicion of gastrointestinal perforation based on a CT scan. The surgeons observed that the stomach was significantly dilated but not perforated. Meanwhile, the patient developed shock and severe acidosis. A further examination confirmed the diagnosis of dapagliflozin-associated eu-DKA. We reviewed the precipitating factors and mechanisms of SGLT2i-associated eu-DKA and discussed the treatment and prevention of this condition. Clinicians need to be alert of the occurrence of SGLT2i-associated eu-DKA in patients treated with this drug in the perioperative period.