SGLT2 Inhibitor Use in Chronic Kidney Disease: Supporting Cardiovascular, Kidney, and Metabolic Health

Abstract

Originally developed for use in type 2 diabetes mellitus (T2DM), sodium-glucose co-transporter-2 (SGLT2) inhibitors demonstrated diverse cardiovascular- and kidney-protective effects in large outcome trials. Their subsequent approval as a treatment for chronic kidney disease (CKD) marked a pivotal shift in the landscape of CKD management. Further to this, the approval of dapagliflozin and empagliflozin for use in patients with CKD with and without T2DM afforded new treatment opportunities for this population. SGLT2 inhibitors provide an effective treatment for CKD with a favorable safety profile. However, their uptake has been slow, especially among patients without T2DM, owing perhaps to a lack of certainty and familiarity among health care professionals. As the landscape of CKD management continues to evolve, health care professionals should remain knowledgeable about these changes, and implement new guideline recommendations promptly to avoid therapeutic inertia. SGLT2 inhibitors are recommended for patients with CKD with or without T2DM and are foundational agents to support cardiovascular, kidney, and metabolic health. In this review, we provide evidence-based answers to questions that may be asked in the clinic regarding the use of SGLT2 inhibitors to treat CKD.

Keywords: Chronic kidney disease; SGLT2 inhibitors; medication; prescribing; sodium-glucose co-transporter-2 inhibitors.

Figure 1

Summary of questions and answers. Abbreviations: CKD, chronic kidney disease; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; RAS, renin–angiotensin system; SGLT2, sodium–glucose co-transporter-2; T2DM, type 2 diabetes mellitus; UACR, urinary albumin-creatinine ratio.

Figure 2

Extrapolation of data from the placebo-controlled DAPA-CKD clinical trial suggests that initiation of SGLT2 inhibitors at a higher eGFR could delay kidney failure by a longer time than initiation at a lower eGFR. Initial eGFR decline over the first 2 weeks was estimated using eGFR slope data from the acute phase of the DAPA-CKD trial. Projections are based on the eGFR from week 2 to end of treatment (DAPA-CKD chronic phase) and assume linear progression of eGFR decline. Example patient with initial eGFR of 60 mL/min/1.73 m² used eGFR slope data from the DAPA-CKD trial subgroup with eGFR ≥ 45 mL/min/1.73 m²; eGFR at the start of the chronic phase: dapagliflozin 10 mg, 56.3 mL/min/1.73 m²; placebo, 59.0 mL/min/1.73 m². Example patient with initial eGFR of 30 mL/min/1.73 m² used eGFR slope data from the DAPA-CKD trial subgroup with eGFR < 45 mL/min/1.73 m²; eGFR at the start of the chronic phase: dapagliflozin 10 mg, 27.4 mL/min/1.73 m²; placebo, 29.6 mL/min/1.73 m². Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; SGLT2, sodium–glucose co-transporter-2.