INTRODUCTION: Sodium Glucose Co-Transporter-2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin are commonly used for type 2 diabetes mellitus treatment. The FDA warns of serious adverse events (AEs) related to the use of SGLT2 inhibitors, such as limb amputations, kidney injury and ketoacidosis

OBJECTIVES: To explore the frequency of the most common AEs associated with SGLT2 inhibitors, and analyze their frequently reported AEs and related patients’ demographics and AE outcomes.

METHODS: A retrospective descriptive study was conducted to analyze all the reported AEs associated with canagliflozin, dapagliflozin, and empagliflozin using the U.S. FDA Adverse Event Reporting System (FAERS) from 2012 to 2022. The total number and most common AEs were calculated annually for each medication. Patients’ demographics data and the AE outcomes were compared and categorized including death, life-threatening, disability, hospitalization, and others.

RESULTS: The most reported AE was Diabetic Ketoacidosis with 16,796 (42%) reported cases, followed by Weight Loss with 5,564 (14%). The least AEs reported were Limb Amputations and fungal infections as they represented only 1,177 (3%) and 360 (1%), respectively, of the reported cases. Total AEs outcomes associated with Canagliflozin were 111,371 reports, which represents 35% of the total reported AEs outcomes. The number of AEs outcomes related to Empagliflozin were 105,031 report (33%). Dapagliflozin reported the least number of AEs outcomes, as there were 104,961 AEs outcomes reports related to the use of this medication (32%).

CONCLUSIONS: The use of canagliflozin was associated with sizable cases of adverse events, followed by empagliflozin, then dapagliflozin. Further pharmacoepidemiologic study is warrant to explore the key health outcomes and safety profiles.