Sodium-glucose cotransporter 2 inhibitors for diabetic kidney disease: a primer for deprescribing

Chronic kidney disease (CKD) is a critical global public health problem associated with high morbidity and mortality, poorer quality of life and increased health care expenditures. CKD and its associated comorbidities are one of the most complex clinical constellations to manage. Treatments for CKD and its comorbidities lead to polypharmacy, which exponentiates the morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown remarkable benefits in cardiovascular and renal protection in patients with type 2 diabetes mellitus (T2DM). The pleiotropic effects of SGLT2is beyond glycosuria suggest a promising role in reducing polypharmacy in diabetic CKD, but the potential adverse effects of SGLT2is should also be considered. In this review, we present a typical case of a patient with multiple comorbidities seen in a CKD clinic, highlighting the polypharmacy and complexity in the management of proteinuria, hyperkalemia, volume overload, hyperuricemia, hypoglycemia and obesity. We review the cardiovascular and renal protection effects of SGLT2is in the context of clinical trials and current guidelines. We then discuss the roles of SGLT2is in the management of associated comorbidities and review the adverse effects and controversies of SGLT2is. We conclude with a proposal for deprescribing principles when initiating SGLT2is in patients with diabetic CKD.