Aim: With the widespread use of SGLT2i, various adverse events (AEs) have been reported. This study aimed to describe the distribution of SGLT2i-related AEs in different systems, quantify the association of important medical events (IMEs) and SGLT2i regimens, and build a signal profile of SGLT2i- induced IMEs. Methods: Data from 2015 Q1 to 2020 Q4 in the FDA Adverse Event Reporting System database (FAERS) were selected to conduct disproportionality analysis. Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to evaluate the correlation between SGLT2i and IMEs. The lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed a signal. For ROR, it was defined a signal if ROR025 over one, with at least 3 cases. Results: A total of 45,771,436 records were involved, including 111,564 records related to SGLT2i, with 38,366 records of SGLT2i-induced IMEs. Overall, SGLT2i was significantly associated with IMEs (IC=0.36, 95% CI: 0.35-0.38; ROR=1.44, 95% CI: 1.42-1.46). Most SGLT2i-related adverse events occurred in monotherapy (92.93%). Diabetic ketoacidosis was the most IMEs. Specifically, acute osteomyelitis has the strongest signal of all SGLT2i (IC025=7.83), and it was unique to canagliflozin. Diabetic ketoacidosis, acute kidney injury, ketoacidosis, Fournier’s gangrene, and euglycemic diabetic ketoacidosis were common to the four FDA-approved SGLT2i. Conclusion: Our study demonstrated that different SGLT2i regimens lead to different important adverse events, but there are overlapping events. Early identification and management of SGLT2i-associated IMEs are essential for clinical practice.