Physicians' Academy for Cardiovascular Education

SGLT2 inhibitor slows eGFR decline in patients with CKD

Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD

Literature - Heerspink HJL, Jongs N, Chertow GM et al., - Lancet Diabetes Endocrinol 2021, 9(11):743-754. doi: 10.1016/S2213-8587(21)00242-4

Introduction and methods

Aim of the study

The SGLT2 inhibitor dapagliflozin lowered the risk of kidney failure in a broad population of patients with chronic kidney disease (CKD) with and without T2DM in the DAPA-CKD trial [1]. In an analysis using a clinical dichotomous outcome, such as kidney failure, the treatment effect depends on the subgroup of patients who progress to these events. Drug efficacy estimations using decline in kidney function over time (GFR slope) are more sensitive to the treatment effect in all patients [2].

In this prespecified analysis of DAPA-CKD, the effect of dapagliflozin on eGFR slope was examined during the acute phase (the first 2 weeks of treatment) and during maintenance phase (starting after 2 weeks of treatment).

Study design

The DAPA-CKD trial was a double-blind, randomized, placebo-controlled trial of 4304 patients with CKD, defined as an eGFR of 25-75 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g. Patients with and without T2DM were included and all patients were on stable ACEi or ARB treatment. They were randomized (1:1) to dapagliflozin or matched placebo. Median on-treatment follow-up was 2.3 years (IQR 1.8-2.6) and the trial was stopped because the primary endpoint was met.


The primary prespecified outcome was the rate of change in eGFR from baseline to the end of treatment.

Main results


This prespecified analysis of DAPA-CKD showed that treatment with dapagliflozin resulted in an acute decline in eGFR, but slowed the subsequent rate of eGFR decline in patients with and without T2DM with a more pronounced effect in patients with T2DM. Moreover, the effect of dapagliflozin on the rate of eGFR decline was larger compared to placebo in patients with higher UACR (more albuminuria) or higher HbAc1 (poorer glycemic control).


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Find this article online at Lancet Diabetes Endocrinol

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