Dapagliflozin reduces hospitalization risk in adults with chronic kidney disease

The SGLT2 inhibitor dapagliflozin was associated with a reduced risk for hospitalization due to any cause in patients with chronic kidney disease with and without type 2 diabetes, according to a post hoc analysis of the DAPA-CKD trial.

Previous data from the randomized, double-blind, placebo-controlled, phase 3 DAPA-CKD trial revealed an “overwhelming benefit” of dapagliflozin in adults with chronic kidney disease (CKD), according to the manufacturer, AstraZeneca. The treatment was shown to reduce worsening renal function or renal death compared with placebo, regardless of patients’ diabetes status.

“Although cardiovascular and kidney outcomes with SGLT2 inhibitors have been studied extensively, there is a paucity of data evaluating the effects of SGLT2 inhibitors on hospitalizations for any cause,” Meir Schechter, MD, PhD, a post-doc fellow at the Diabetes Clinical Research Center at Hadassah Medical Center in Israel, and colleagues wrote in Annals of Internal Medicine.

For the current analysis, Schechter and colleagues examined data from 4,304 patients (mean age, 61.8 years; 33.1% women) with CKD to investigate the effects of dapagliflozin (10 mg once daily) vs. placebo on first and subsequent hospitalizations.

Among the 2,906 participants with type 2 diabetes, 1,455 received dapagliflozin and 1,451 received placebo. Of those without type 2 diabetes, 697 received dapagliflozin and 701 received placebo.

Over a median follow-up period of 2.4 years, Schechter and colleagues identified 2,072 hospitalizations among 1,224 (28.4%) participants.

Dapagliflozin was associated with a lower risk for first hospitalization (HR = 0.84; 95% CI, 0.75-0.94) and all hospitalizations (rate ratio [RR] = 0.79; 95% CI, 0.7-0.89) compared with placebo, according to the researchers. At least one hospitalization was reported in 26.3% of patients in the dapagliflozin group, yielding an event rate of 143.7 per 1,000 person-years, and 30.6% of patients in the placebo group, for an event rate of 171.9 events per 1,000 person-years.

Schechter and colleagues further reported that, compared with placebo, dapagliflozin reduced the risk for hospitalizations due to cardiac disorders (RR = 0.67; 95% CI, 0.53-0.86), renal and urinary disorders (RR = 0.61; 95% CI, 0.46-0.79), metabolism and nutrition disorders (RR = 0.61; 95% CI, 0.41-0.91) and neoplasms (RR = 0.62; 95% CI, 0.39-0.96).

“There was no evidence that the effects of dapagliflozin on first and all hospitalizations varied by baseline presence of type 2 diabetes,” they wrote.

Since the study was conducted as a post hoc analysis, Schechter and colleagues noted that it “should be viewed as hypothesis-generating.” Still, the researchers said the findings have “major clinical relevance,” as hospitalizations contribute to CKD burden and reduce health-related quality of life among patients.

“These findings highlight additional benefits of dapagliflozin beyond those seen for cardiovascular and kidney events, all-cause and cause-specific mortality, eGFR slope and albuminuria and should be considered when evaluating the totality of evidence favoring provision of dapagliflozin to patients with CKD,” they wrote.