Postmortem analysis of the DECLARE-TIMI 58 study showed that dapagliflozin can reduce the risk of DKD in patients with T2DM who have cardiovascular risk factors!

At present, with the increasing prevalence of diabetes, the aging of the population, lifestyle changes and other factors, the number of patients with diabetic nephropathy (DKD) is increasing
.
So, apart from lifestyle interventions, are there any drugs that can prevent chronic kidney disease (CKD) in people with diabetes?

In October 2022, a post-mortem analysis of the DECLARE-TIMI 58 study published in Diabetes Care concluded that dapagliflozin was able to delay the decline in renal function in patients with type 2 diabetes mellitus (T2DM) with cardiovascular risk factors, suggesting that dapagliflozin played a role in the early prevention of DKD and could be included in the primary prevention strategy
of CKD in patients with T2DM.

Study the design

Methods

The DECLARE-TIMI 58 study included 17,160 patients with T2DM who
were at high risk of arteriosclerotic cardiovascular disease (ASCVD) or ASCVD.
At the time of enrollment, patients were between 6.
5% and 12% at baseline glycosylated hemoglobin (HbA1c), and the creatinine clearance ≥ 60 ml/min
.
Patients were divided into a 1:1 ratio of dapagliflozin (10 mg/day) and a control group
.

This post-mortem analysis was mainly based on the analysis
of patients after KDIGO's CKD risk stratification.
The preset renal-specific composite endpoint was to estimate a sustained decrease in glomerular filtration rate (eGFR) ≥40%, or eGFR <60 ml/min/1.
73 m2, end-stage renal disease (ESKD) or renal-related death<b11>.
Other secondary endpoints were the incidence of eGFR decline in patients with different CKD risk stratification, and changes in eGFR slope in
patients from 6 months to 4 years and from baseline to 4 years.

Results of the study

Results

In the DECLARE-TIMI 58 study, according to CADGEO's CKD risk stratification indicator, 10,958 patients (65.
1%) were low-risk patients, 4243 (25.
2%) were at moderate risk, 1403 (8.
3%) were high-risk people, and 238 (1.
4%) were extremely high-risk people
.
The risk population composition of the dapagliflozin group and the control group was similar (P = 0.
923).

Table 1 Specific ratio of renal-specific composite endpoints to HR after risk stratification

In addition, dapagliflozin delayed the risk of eGFR decline compared with the control group, with eGFR reduction rates ≥ 57%, ≥50%, ≥40%, and ≥30% HRs of 0.
52, 0.
57, 0.
55, and 0.
70 (P<0.
05),<b10> respectively.

Compared with the control group, dapagliflozin delayed the decline of eGFR, whether for a period of 6 months to 4 years (0.
87 ml/min/1.
73 ㎡ between groups) or a baseline to 4 years period (inter-group difference: 0.
55 ml/min/1.
73 ㎡; P<0.
0001), the variation in eGFR in the dapagliflozin group was small<b10>.

The control group had a higher rate of eGFR decline compared to the dapagliflozin group, whether it was between 6 months and 4 years (0.
87 ml/min/1.
73 ㎡ difference between groups) or from baseline to 4 years (difference between groups: 0.
55 ml/min/1.
73 ㎡; P<0.
0001), there was little difference in the variation of eGFR in patients in the dapagliflozin<b10> group.

Overall, in patients with T2DM who have co-existing cardiovascular risk factors, dapagliflozin can reduce the incidence of renal disease in patients
.
This post-mortem analysis showed that dapagliflozin could be used as a primary prevention strategy
for CKD in patients with T2DM.