Physicians' Academy for Cardiovascular Education

SGLT2i reduces clinical outcomes in CKD patients with and without T2DM

Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial

Literature - Wheeler DC, Stefánsson BV, Jongs N et al., - Lancet Diabetes Endocrinol 2021; 9: 22–31

Introduction and methods

SGLT2 inhibitors slow down the rate of decline of eGFR and albuminuria in patients with type 2 diabetes [1] and in patients with chronic kidney disease and type 2 diabetes [2]. Clinical studies and experimental data on use of SGLT2 inhibitors support a beneficial hemodynamic effect in the kidneys. This suggests that use of SGLT2 inhibitors results in beneficial kidney outcomes independent of effects on glucose and therefore in patients with CKD with etiologies other than T2DM [3,4].

In the DAPA-CKD trial, dapagliflozin reduced risk of kidney failure, death from CV causes or hospital admission for heart failure and death from any cause in a broad group of individuals with CKD [5].

In this prespecified analysis of DAPA-CKD, it was investigated whether the presence or absence of type 2 diabetes at baseline and the underlying etiology of kidney disease modified the effects of dapagliflozin on clinical outcomes.

Patients in the DAPA-CKD trial were randomized to dapagliflozin once daily or matching placebo in a 1:1 ratio, in addition to standard care. At screening visit diagnosis of kidney disease was recorded with the following categories: diabetic nephropathy, chronic glomerulonephritides (a subgroup of IgA nephropathy was analyzed separately), ischemic or hypertensive CKD, other or unknown causes of CKD. Primary outcome was a composite of sustained decline of 50% or more in eGFR, onset of end-stage kidney disease, or death from kidney or CV causes. In the main trial, 4303 patients were enrolled with a mean eGFR of 43 ml/min/1.73m2, a median UACR of 949 mg/g, who were followed for a median of 2.4 years (IQR 2.0-2.7). 32% Of patients did not have T2DM and 396 participants with T2DM had CKD due to other causes than diabetic nephropathy.

Main results


This prespecified analysis of the DAPA-CKD trial demonstrated that the reduction of major adverse kidney and CV outcomes by dapagliflozin when compared to placebo in patients with CKD was irrespective of diabetes status and the underlying cause of CKD.


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Find this article online at Lancet Diabetes Endocrinol

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