SGLT2 Inhibitors: Risks and Benefits

Background: Inconsistent meta-analysis results and the increased risk of co-morbid conditions in type two diabetes make it challenging to distinguish if adverse effects of Fournier’s Gangrene, acute kidney injury, ketoacidosis, genitourinary fungal infections, amputations, and bone fractures are attributed to SGLT2 inhibitors. Methods: This is a retrospective cohort study that calculates the relative risk and hazard ratio using the Food and Drug Administration Adverse Event Reporting System to compare the users of metformin and the SGLT2 inhibitors for adverse events. The Medical Expenditure Panel Survey database was used to generate total users of dapagliflozin, empagliflozin, canagliflozin, and metformin from the years 2014-2021. Results: We observed an average increased risk of Fournier’s Gangrene by 156-fold, ketoacidosis by 67-fold, genitourinary fungal infections by 185-fold, amputations by 277-fold, and bone fractures by 15-fold compared to individuals taking metformin. Canagliflozin had the highest increased risk in all categories except for Fournier’s Gangrene, and empagliflozin did not have an increased relative risk of acute kidney injury. Conclusion: We measured an increase in complications of patients on SGLT2 inhibitors, especially canagliflozin, compared to patients on metformin. We as health providers should re-evaluate our patients with increased risks of these complications and reassess if the cardiovascular benefits outweigh the possible dangerous side effects.