Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors: Are They All the Same? A Narrative Review of Cardiovascular Outcome Trials

Clinically important improvements in cardiovascular risk factors and adverse cardiovascular, heart failure and renal outcomes have been observed in numerous cardiovascular outcome trials (CVOTs) investigating the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors over the last 5 years. However, differences in study outcomes between the various SGLT2 inhibitor CVOTs are often challenging to interpret because of differences in the study design, participant characteristics and primary outcomes of the various trials. In clinical practice, this frequently challenges the clinician when choosing between the different SGLT2 inhibitors for a patient with type 2 diabetes and various cardiovascular or renal comorbidities. Discussion around the choice of SGLT2 inhibitor has been again revived by the recent publication of results from the VERTIS-CV, EMPEROR-reduced and DAPA-CKD trials investigating cardiovascular, heart failure and renal outcomes associated with various SGLT2 inhibitors. This narrative review gives an overview of the mechanism of action and differences in the underlying pharmacology of the various SGLT2 inhibitors and discusses the key cardiovascular, heart failure and renal outcomes from completed CVOTs for SGLT2 inhibitors. Discussion highlights important differences in the study design and participant characteristics which limit the comparison of trials and medications within this drug class.