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Objective To evaluate post-marketing safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i), including dapagliflozin, canagliflozin and empagliflozin. Methods Reporting odds ratio (ROR) algorithm was adopted to investigate signals of all adverse drug event (ADE) reports submitted to Food and Drug Administration adverse event reporting system from 2012 Q4 to 2017 Q2. Results SGLT2i were recorded in 24 956 reports as suspects (4 699 reports were attributed to dapagliflozin, 15 980 to canagliflozin and 4 277 to empagliflozin), among which 13 905 (55.72%) were serious adverse events and the most frequently reported ADE was diabetes ketoacidosis (2 594, 10.39%). Statistically significant ROR emerged for the following ADEs renal impairment (acute kidney injury, decrease of glomerularfiltration rate, increase of blood creatinine), ketoacidosis (diabetes ketoacidosis), genital infection (genital mycotic infection, balanoposthitis, vulvovaginal mycotic infection, vaginal infection), urinary tract infection (pyelonephritis, urosepsis), hypoglycemia. Furthermore, several new ADE signals for dapagliflozin, canagliflozin and empagliflozin were detected: lactic acidosis (ROR=3.52, 95%CI 2.18-5.67; ROR=3.74, 95%CI 2.90-4.81; ROR=3.41, 95%CI 2.05-5.66, respectively), pancreatitis (ROR=4.07, 95%CI 3.04-5.44; ROR=6.37, 95%CI 5.60-7.24; ROR=6.06, 95%CI 4.72-7.80, respectively). Potential signals of hyperkalaemia (ROR=3.82, 95%CI 2.56-5.72; ROR=3.15, 95%CI 1.98-5.00, respectively) and toe amputation (ROR=7.37, 95%CI 3.06-17.77; ROR=13.02, 95%CI 6.48-26.16, respectively) were also discovered for dapagliflozin and empagliflozin (labeled in canagliflozin instructions). No fracture associated with SGLT2i agents was identified. Conclusions In addition to known safety issues such as urinary/genital tract infections, renal impairment, ketoacidosis and hypoglycemia, potential risks of lactic acidosis and pancreatitis should also be noted during the clinical application of SGLT2i. [ABSTRACT FROM AUTHOR]