OBJECTIVES:   Sodium-glucose transport protein 2 (SGLT-2) inhibitors demonstrate favorable efficacy profiles that include glycemic control and reductions in body weight but are associated with adverse events including ketoacidosis, urinary tract infections, candida vulvovaginitis, and hypoglycemia. This comparative safety and efficacy analysis is designed to compare relevant clinical endpoints in the prescribing information labels of available SGLT-2 inhibitors and identify the most prevalent and clinically significant outcomes which are crucial in the management of patients with type 2 diabetes (T2D).  METHODS: A multivariate analysis was undertaken using clinical endpoints from product information labels (n=3; canaglifozin, dapagliflozin, empagliflozin) of available SGLT-2 inhibitors. Compounds with 24- to 26-week, placebo-controlled endpoint data were analyzed. Efficacy endpoints included change from baseline in hemoglobin A1c (%) and body weight (kg). The safety endpoints included percentage of patients reporting adverse events, including urinary tract infections, female genital mycotic infections, and incidence of hypoglycemic events (%). RESULTS: No compound outperformed competitors in all predefined outcome measures after 24- to 26- weeks of treatment. Canagliflozin 300 mg + metformin reported the greatest reduction in body weight (-4.07 kg) and the greatest reduction in HbA1c (-1.06%). However, canagliflozin 300 mg + metformin (4.6%) reported the greatest incidence of hypoglycemia events and the greatest incidence of urinary tract infections (11.4%) after 26 weeks. CONCLUSIONS: Despite the robust efficacy profiles presented in this analysis, physicians should consider the potential adverse events associated with each SGLT-2 inhibitor before deciding on a treatment regimen. Diabetes treatment regimens are often highly individualized, and healthcare providers must weigh the benefits of any treatment with its attendant risks. Of special concern among SGLT-2 inhibitors is the recent US FDA warning of increased risk for diabetic ketoacidosis associated with these compounds.