Empagliflozin and the Diabetic Kidney: Pathophysiological Concepts and Future Challenges

Chronic kidney disease is a serious co-morbidity of patients with diabetes, which amplifies the global burden of this disease, affects the quality of their life, and significantly increases both morbidity and mortality. Therefore, there is a high unmet clinical need to develop therapeutic strategies in order to prevent, delay, or even reverse its evolution. EMPA-REG OUTCOME trial has fundamentally changed the therapeutic landscape of patients with type 2 diabetes and signified a new era in which treatment approaches should be tailored based on end-organ protection and patient comorbidities rather than focusing only on their antihyperglycemic effects. This paper discusses the seminal EMPA-REG OUTCOME trial, focusing on its renal outcomes, and explores extensively the possible pathophysiological mechanisms governing the nephroprotective activity of empagliflozin both in in vitro and in vivo (animal models and humans) studies during a diabetic state. It also discusses the safety of empagliflozin therapy and its future role in order to ameliorate the global burden of CKD both in patients with and without diabetes.