Dapagliflozin excels in chronic kidney disease, even in patients without diabetes

Adding dapagliflozin to standard of care (SOC) significantly reduces the risk of worsening kidney function, death due to kidney or cardiovascular (CV) disease, and all-cause mortality compared with SOC alone in patients with chronic kidney disease (CKD), regardless of whether they have type 2 diabetes (T2D), reveals the DAPA-CKD* trial — showing dapagliflozin charting new territories from diabetes to the renal realm.   

“Previously we’ve seen benefits with SGLT2** inhibitors on heart failure [HF], CV events, and renal outcomes in patients with diabetes and HF. But what would we see in patients with CKD?” said session chair Professor Rory Collins from University of Oxford, UK during the opening of the “eagerly-awaited” session.

“We found that dapagliflozin delayed the initiation of dialysis and reduced the number of deaths. The effect of dapagliflozin was consistent in patients with and without T2D,” summed up principal investigator Professor Hiddo Heerspink of University Medical Centre Groningen, the Netherland, during the online press conference.

“The DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment option for patients with CKD,” he highlighted.

After a median follow-up of 2.4 years, dapagliflozin led to a 39 percent reduction in the composite primary outcome of worsening kidney function*** or deaths due to renal or CV disease compared with placebo, added on to a background therapy for controlling CKD (hazard ratio [HR], 0.61; p=0.000000028). The difference between groups was highly significant statistically with a number needed to treat of 19. [ESC 2020, hot line session]

Notably, the benefit from dapagliflozin was not only limited to the two-third of patients with diabetes (HR, 0.64), but also extends to those without diabetes (HR, 0.50).

All three secondary endpoints were also significantly lower with dapagliflozin vs placebo: worsening renal function or renal death (HR, 0.56; p<0.0001), hospitalization for HF or CV death (HR, 0.71; p=0.0089), and all-cause mortality (HR, 0.69; p=0.0035).

In addition, the findings were consistent across all prespecified subgroup analyses, in favour of dapagliflozin.  

Participants in the global DAPA-CKD trial were 4,304 patients (mean age 61.8 years, 66.9 percent male) with CKD (eGFR^# of 25–75 mL/min/1.73 m²; UACR 200–5,000 mg/g). They were randomized to 1:1 to once-daily dapagliflozin 10 mg or placebo, in addition to standard of care therapies comprising renin-angiotensin system-blocking medications (ACE inhibitor or ARB). One-third of the patients did not have diabetes (32.5 percent).

What’s next?

While the renal outcomes were largely similar with previous studies on other members of the SGLT2 inhibitor class such as CREDENCE and EMPA-REG OUTCOME, “what DAPA-CKD adds is that dapagliflozin reduces the risk of renal outcomes in patients with CKD irrespective of the presence or absence of diabetes,” pointed out invited discussant Dr Diederick Grobbee of University Medical Center Utrecht, the Netherlands.

“[We know that] SGLT2 inhibitors are beneficial in diabetes and HF, now we know they are beneficial in CKD, what’s next for them?” asked Collins.

With the far-reaching benefits of dapagliflozin seen on top of guideline-recommended treatment of CKD (ACE inhibitor or ARB), Grobbee said “You may wonder if this is indeed the way to go: add drug on drug on drug, or at some point we might wish to perhaps replace one for another that’s more beneficial — but that’s for future research.”