The SGLT2 inhibitor dapagliflozin has been found to steadily lowered cardiovascular events irrespective of kidney function and albuminuria status at the baseline in patients with type 2 diabetes mellitus. The most significant benefit was achieved in individuals with the most severe kidney disease, as seen in a prespecified secondary analysis of the DECLARE-TIMI 58 trial. 

The secondary analysis of the data from the DECLARE-TIMI 58 showed that the more CKD markers the patients have, the higher were the rates of the dual primary endpoint of cardiovascular events; major adverse CV events (MACE; 7.5 percent, 11.6 percent, and 18.9 percent for zero, one, and two markers, respectively), and the composite of CV death or hospitalization for heart failure (HHF) (3.9 percent, 8.3 percent, and 17.4 percent, respectively) at four years, among patients in the placebo group. 

In this secondary analysis, the trial participants were classified depending on the number of CKD markers; two markers if they had both reduced eGFR (<60 mL/min/1.73m²) and albuminuria (UACR ≥30 mg/g); one of them had either marker and none if their eGFR was ≥60 mL/min/1.73m²) and UACR< 30 mg/g. 

In the study, dapagliflozin demonstrated an increased relative risk reduction in the two primary endpoints and its components of cardiovascular death and HHF compared with placebo. The benefits were seen to persist across various subgroups irrespective of CKD markers (p>0.24 for interaction). 

In the same analysis, reductions in the absolute risk of the composite of cardiovascular death or HHF were more in patients with more CKD markers; 8.3 percent for two markers, -1.0 percent for one marker, and -0.5 percent for zero markers (p=0.02 for interaction). 

It is well known that cardiovascular disease can increase the load on the kidney and cause kidney-related complications and vice versa. In this context, SGLT2 inhibitors can block this cycle through cardiorenal protective effects. The results from this secondary analysis of the DECLARE-TIMI 58 CV outcome trial have been further strengthened by other trial results, such as the CREDENCE trial for the benefits of SGLT2 inhibitors in patients with CKD. In comparison, the population enrolled in 

DECLARE-TIMI 58 trial had more preserved kidney function at baseline.

Reference

1. Internet resource. Toh P. Dapagliflozin cuts CV events even in patients with severe kidney disease. CIMS Endocrinology. 3 May 2021. Accessed on 21 June 2021 from https://specialty.mims.com/topic/dapagliflozin-cuts-cv-events-even-in-patients-with-severe-kidney-disease-?channel=endocrinology&elq_mid=55671&elq_cid=42767.