Physicians' Academy for Cardiovascular Education

Consistent effect of SGLT2i on CV outcomes across eGFR and UACR groups in T2DM

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized Clinical Trial

Literature - Zelniker TA, Raz I, Mosenzon O et al. - JAMA Cardiol 2021, DOI: 10.1001/jamacardio.2021.0660

Introduction and methods

Glucosuria by an SGLT2 inhibitor is attenuated in patients with kidney failure and therefore the glucose-lowering efficacy in these patient is reduced [1], but benefit for HF hospitalization (HHF) by SGLT2i was greatest among patients with lower baseline eGFR in a recent meta-analysis [2]. These findings support the paradigm shift from a glucocentric approach to a broader CV risk reduction approach for the management of T2DM patients.

This study is a prespecified secondary analysis of the DECLARE-TIMI 58 trial to examine CV efficacy and safety of dapagliflozin across subgroups of kidney function and albuminuria status [3-5]. Dapagliflozin reduced the risk of CV death and HHF compared to placebo in 17,160 T2DM patients with multiple risk factors for or established ASCVD [5]. It is important to investigate the safety profile of dapagliflozin in CKD patients, as this cohort is susceptible to adverse events.

Patients with a creatinine clearance below 60 mL/min at screening were excluded from the trial. Primary efficacy outcomes of this analysis were composite of CV death of HHF and of MACE. Safety outcomes of interest included major hypoglycemia, amputation, diabetic ketoacidosis, and fracture. Patients were categorized according to baseline eGFR (<60 vs ≥60 mL/min/1.73 m2 and baseline urinary albumin to creatinine ratio (UACR; <30 vs ≥30 mg/g) and categorically ranked by number of CKD markers (0,1 or 2).

Main results


This secondary analysis of the DECLARE-TIMI 58 trial showed that relative risk reduction of CV outcomes (composite of CV death or HHF) by dapagliflozin was irrespective of baseline eGFR and albuminuria status in T2DM patients with ASCVD or at high risk for ASCVD. Patients with more markers of CKD had a greater absolute risk reduction of CV outcomes by dapagliflozin. These favorable effects were not counterbalanced by adverse events in those with lower eGFR or albuminuria.


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Find this article online at JAMA Cardiol

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