Individuals With Chronic Kidney Disease Qualifying for SGLT-2 Inhibitors in the United States and EMPA-KIDNEY Generalizability

The EMPA-KIDNEY (Study of Heart and Kidney Protection with Empagli ﬂ ozin) trial 1 is the latest in a series of 4 randomized controlled trials of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with chronic kidney disease (CKD) 1-4 showing outcome bene ﬁ ts. EMPA-KIDNEY was a global randomized controlled trial of empagli ﬂ ozin in patients with CKD. Building on previous trials, EMPA-KIDNEY evaluated the broadest range of CKD patients, enrolling patients who had an estimated glomerular ﬁ ltration rate (eGFR) down to $ 20 mL/min/1.73 m 2 , and also extending to patients with and without diabetes at risk for CKD progression. With EMPA-KIDNEY showing a bene ﬁ t in composite primary outcome for progression of kidney disease in such a wide range of CKD patients, SGLT-2 inhibitors are likely to be indicated for a broader CKD population in the United States. We estimated a benchmark for national implementation by determining the number of U

The EMPA-KIDNEY (Study of Heart and Kidney Protection with Empagliflozin) trial 1 is the latest in a series of 4 randomized controlled trials of sodiumglucose cotransporter-2 (SGLT-2) inhibitors in patients with chronic kidney disease (CKD) 1-4 showing outcome benefits.EMPA-KIDNEY was a global ran- We included nonpregnant individuals $18 years with an eGFR of $20 but <45 mL/min/1.73m 2 regardless of level of albuminuria or eGFR of $45 but <90 mL/min/1.73m 2 with a urine albumin-creatinine ratio (UACR) of $200 mg/g.Patients were required to be treated with a renin-angiotensin system inhibitor.We excluded those with type 2 diabetes mellitus who had eGFR >60 mL/min/1.73m 2 and prior atherosclerotic cardiovascular disease, defined as history of myocardial infarction, angina, or stroke.

CREDENCE (Canagliflozin and Renal Events in
Compared with EMPA-KIDNEY trial participants, the eligible U.S. population was older (mean age: 71.1 AE 0.6 vs 63.9 in the trial), had higher mean eGFR (44.5 AE 1.0 vs 37.4 mL/min/1.73m 2 ), and had a higher building upon what SCORED had shown in patients Research Letter domized controlled trial of empagliflozin in patients with CKD.Building on previous trials, EMPA-KIDNEY evaluated the broadest range of CKD patients, enrolling patients who had an estimated glomerular filtration rate (eGFR) down to $20 mL/min/1.73m 2 , and also extending to patients with and without diabetes at risk for CKD progression.With EMPA-KIDNEY showing a benefit in composite primary outcome for progression of kidney disease in such a wide range of CKD patients, SGLT-2 inhibitors are likely to be indicated for a broader CKD population in the United States.We estimated a benchmark for national implementation by determining the number of U.S. individuals eligible for SGLT-2 based on the 4 major trial eligibility criteria.We further characterized the breakdown of individuals eligible for empagliflozin by Kidney Disease Improving Global Outcomes classification.EMPA-KIDNEY enrollment criteria were applied to the National Health and Nutrition Examination Survey (NHANES) (2009-2018).NHANES is designed to represent the U.S. population by using multistage, stratified, clustered samples of the civilian noninstitutionalized population.NHANES was approved by the National Center for Health Statistics Institutional Review Board.
Diabetes with Established Nephropathy Clinical Evaluation) trial, DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial, and SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) trial enrollment criteria were also separately applied. 2-4Finally, the total number of U.S. individuals meeting any of the 4 trial criteria was estimated.Analyses were conducted with R 4.0.5 and survey-weighting design was used to determine national projections.
with UACR <30 mg/g (45.8% AE 3.1% vs 20.1%).The U.S. population also had a higher proportion of women (58.1% AE 2.6% vs 33.2%).Our analysis suggests that over 5 million U.S. individuals with CKD may be eligible for SGLT-2 inhibitors by major trial criteria.EMPA-KIDNEY demonstrated many patients with CKD could benefit from therapy, including those with eGFRs down to 20 mL/min/1.73m 2 , with our analysis estimating 3 million U.S. individuals eligible.Our analysis also shows up to 367,756 individuals with eGFR <30 mL/min/1.73m 2 eligible for empagliflozin in the U.S.-a reminder to clinicians to keep this atrisk population in mind for SGLT-2 inhibitor initiation.Furthermore, EMPA-KIDNEY established the benefits of SGLT-2 inhibition for patients with lower levels of albuminuria even without diabetes,1,5

FIGURE 1
FIGURE 1 Individuals With Chronic Kidney Disease Qualifying for SGLT-2 Inhibitors in the United States