Dapagliflozin Lowers Hospitalization Risk in Patients With CKD Despite Diabetes Status

Among patients with chronic kidney disease (CKD), both with and without type 2 diabetes, dapagliflozin was effective in reducing the risk of hospitalization for any cause, according to a study published in Annals of Internal Medicine.

Acute hospitalizations are more common in patients with CKD. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have previously been identified as being able to reduce the risk of cardiovascular outcomes and stop the progression of CKD in patients with type 2 diabetes. This post hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial aimed to assess the effects of dapagliflozin on first hospitalizations and all hospitalizations in patients with CKD who did or did not have a diagnosis of type 2 diabetes.

The DAPA-CKD trial was a double-blind, multicenter, randomized, placebo-controlled trial that was designed to evaluate the effect of dapagliflozin on kidney and cardiovascular outcomes. Participants were 18 years or older, had a baseline estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73 m², and had a urinary albumin-creatinine ratio (UACR) of 200 to 5000 mg/g.

Patients with type 1 diabetes, polycystic kidney disease, lupus nephritis, or antineutrophil cytoplasmic antibody–associated vasculitis, as well as patients receiving immunotherapy for other primary or secondary kidney diseases within 6 months, were excluded. All participants received a stable dose of angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker at least 4 weeks before randomization.

All 4304 included patients were randomized into 2 groups, 1 that received 10 mg of dapagliflozin once daily and 1 group that received a placebo. Treatment continued until the occurrence of diabetic ketoacidosis, pregnancy, or trial completion. Hospitalizations were included if they started between the randomization date and the censoring date of April 3, 2020.

There were 2072 hospitalizations, 1224 (59.1%) of which were prolonged or ended in death, over a median of 2.4 years. Of the 4304 patients, 1224 (28.4%) had at least 1 hospitalization in the follow-up period, 808 (18.3%) had at least 1 hospitalization that was prolonged or ended in death, and 453 (10.5%) had 2 or more hospitalizations; the median duration of hospitalization was 7 days.

There were 566 patients (26.3%) who had at least 1 hospitalization in the dapagliflozin group, whereas 658 (30.6%) patients in the placebo group had at least 1 hospitalization, with an overall HR of 0.84 (95% CI, 0.75-0.94) for the former group. Dapagliflozin reduced the risk for a prolonged hospitalization or one ending in death (HR, 0.83; 95% CI, 0.72-0.95), the composite of first hospitalization or death (HR, 0.83; 95% CI, 0.75-0.93), and all hospitalizations or death (rate ratio [RR], 0.79; 95% CI, 0.70-0.89).

The effect of dapagliflozin did not vary between first and all hospitalizations. Dapagliflozin was found to be more effective at preventing hospitalizations for patients 65 years or younger compared with those older than 65 years. Compared with the placebo group, there was a mean increase of 3.3 days alive and out of the hospital per person-year associated with dapagliflozin.

Among the 4304 patients, 8.8% had at least 1 hospitalization related to infections and infestations; 7.5%, cardiac disorders; and 5.8%, renal and urinary disorders. Dapagliflozin reduced the rate of admissions 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 were some limitations to this study. This study should be viewed as hypothesis generating due to its post hoc nature. Hospitalizations were reported by site investigators and not centrally adjudicated. Partial unmasking of the participants may have happened by investigators noting the patients’ signs or symptoms, which may have biased their reporting of all-cause or cause-specific hospitalizations. Length of hospital stay can be affected by multiple factors other than disease severity.

The researchers of this study concluded that the SGLT2 inhibitor dapagliflozin was effective in reducing the risk of hospitalization in patients with CKD with or without a diagnosis of type 2 diabetes. Dapagliflozin also increased the number of days alive and out of the hospital.

Reference

Schechter M, Jongs N, Chertow GM, et al. Effects of dapagliflozin on hospitalizations in patients with chronic kidney disease: a post hoc analysis of DAPA-CKD. Ann Intern Med. Published online December 6, 2022. doi:10.7326/m22-2115