Risk factors of dapagliflozin-associated diabetic ketosis/ketoacidosis in patients with type 2 diabetes mellitus: A matched case-control study

Objective: To investigate the risk factors of dapagliflozin-associated diabetic ketosis/ketoacidosis (DK/DKA) in patients with type 2 diabetes mellitus (T2DM).Research Design and Methods: A case-control study was conducted in a general hospital in China from 2018 to 2021. T2DM patients who developed DK/DKA after dapagliflozin treatment were identified. Each patient in the DA/DKA group was matched with a patient in the non-DK/DKA group in terms of the baseline characteristics. Receiver operating characteristic (ROC) curve analysis and logistic regressions were performed.Results: Out of 1,684 hospitalized patients taking dapagliflozin, 170 were diagnosed with dapagliflozinassociated DK/DKA. A total of 137 cases were matched with 137 controls. The mean time-to-onset (TTO) of DK/DKA was 28.59 days. Logistic regression showed that current drinking (OR = 7.656, p < 0.001), T2DM duration >= 7.625 years (OR = 2.399, p = 0.017), acute ST-elevations myocardial infarction (STEMI) (OR = 12.770, p = 0.028), acute infection (OR = 2.862, p = 0.043), insulin dose reduction/cessation before dapagliflozin exposure (OR = 6.751, p < 0.001), and a major plus or major operation (OR = 2.652, p = 0.022) were risk factors for dapagliflozin-associated DK/DKA. Furthermore, T2DM duration >= 7.625 years (p = 0.046) and acute STEMI (p < 0.001) were independently associated with more severe DK/DKA.Conclusion: Current drinking, long T2DM duration, STEMI, acute infection, insulin deficiency, and major operation are the risk factors associated with DK/DKA in T2DM patients. Furthermore, long T2DM duration and STEMI were associated with more severe DK/DKA situations.