Ertugliflozin preserves kidney function in patients with diabetes, cardiovascular disease
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The SGLT2 inhibitor ertugliflozin shows promise for preserving kidney function in patients with type 2 diabetes and atherosclerotic cardiovascular disease, results of a placebo-controlled trial suggested.
Further, investigators found the drug slowed eGFR decline for all study participants regardless of kidney status at baseline.
Assessed kidney function loss with eGFR slope
“Recent trials have used the risk of reaching a sustained significant percent decline in eGFR over time as a surrogate for clinical endpoints in kidney outcome studies,” David Cherney, PhD, of the University of Toronto, and colleagues wrote. “There is an emerging consensus that a [at least a] 40% decline in eGFR is the most appropriate measure under most circumstances. However, these surrogates may not be applicable to all populations, interventions, or in early stages of kidney disease.
Another method to assess significant kidney function loss over time involves the use of eGFR slope as a surrogate for kidney failure. Using eGFR slope as a surrogate for [chronic kidney disease] CKD progression in clinical studies has been supported by National Kidney Foundation working groups and has the added benefit of allowing for a smaller sample size. In analyses by Levey, Inker and others, a treatment effect of [at least] 0.75 mL/min per 1.73 m2 per year on slope over 3 years in sufficiently powered studies predicts a clinical benefit on CKD progress with at least 96% probability.”
Contending that “the identification of reasonable clinical surrogates for kidney protection is a major nephrology research priority,” Cherney and colleagues sought to assess the impact of ertugliflozin on acute and chronic eGFR slopes, rather than only considering “more traditional definitions of kidney function loss.”
To this end, researchers randomized 8,246 patients with a baseline eGFR of at least 30 mL/min/1.73 m2 to placebo or ertugliflozin. Based on KDIGO categories, 48.8% were at low risk for CKD, 32% were at moderate risk and 19.3% were at high risk.
Ertugliflozin preserved kidney function
Patients were followed for a median of 3 years, after which researchers observed a clinically relevant preservation of eGFR with ertugliflozin compared with placebo starting after 6 weeks (before 6 weeks, ertugliflozin induced a greater degree of eGFR decline, which the researchers expected).
Specific findings showed that, during weeks 6 to 52, the least square mean eGFR slope per year was -0.12 mL/min/1.73 m2 for the placebo group and 1.62 mL/min/1.73 m2 for ertugliflozin group, leading to a difference of 1.74 mL/min/1.73 m2.
For weeks 6 to 156, least square mean eGFR slopes per year were -1.51 mL/min/1.73 m2 and -0.32 mL/min/1.73 m2 for the placebo group and the ertugliflozin group, respectively.
During weeks 0–156, researchers observed a placebo-adjusted difference in least square mean slope of 1.06 mL/min/1.73 m2.
“In this analysis from the VERTIS CV study, ertugliflozin had a favorable effect on eGFR change over time compared with placebo, reflected by a greater preservation of kidney function during the chronic treatment period after 6 weeks,” Cherney and colleagues concluded, adding that the analyses reveal a potential for kidney function benefits with SGLT2 inhibition, “even in a cohort that had a relatively low overall risk for CKD progression.”
“Protection against CKD progression may be especially important in light of the close relationship between kidney function loss and the development of heart failure,” the researchers wrote.
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