Dapagliflozin Curbs Albuminuria in CKD With or Without Diabetes

NEW YORK (Reuters Health) – In patients with chronic kidney disease (CKD), with or without type 2 diabetes, the SGLT2 inhibitor dapagliflozin reduced albuminuria, according to data from the DAPA-CKD trial.

“The effect was greater in patients with type 2 diabetes compared to those without type 2 diabetes,” Dr. Hiddo Heerspink of University Medical Centre Groningen in the Netherlands told Reuters Health by email. “The similar efficacy in patients with and without type 2 diabetes on clinical outcomes suggests that part of dapagliflozin’s protective effect is mediated through pathways unrelated to albuminuria reduction.”

As reported in The Lancet Diabetes and Endocrinology, the trial protocol defined CKD as an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 and 5,000.

A total of 4,304 participants in 21 countries received dapagliflozin 10 mg or placebo once daily and were followed for a median of 2.4 years. The median UACR was 949.

Notably, the trial was stopped early for overwhelming efficacy based on a recommendation of the Independent Data Monitoring Committee.

In this prespecified analysis, overall, dapagliflozin reduced the geometric mean UACR by 29.3% compared to placebo.

In patients with type 2 diabetes, relative to placebo, treatment with dapagliflozin resulted in a geometric mean percentage reduction of 35.1%, versus a reduction of 14.8% in patients without type 2 diabetes.

Among 3,860 patients with a UACR of 300 or greater at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio, 1.81).

Among 3,820 patients with a UACR less than 3,000 at baseline, dapagliflozin decreased the risk of progression in UACR stage (0.41).

Larger reductions in UACR at day 14 of dapagliflozin treatment were significantly associated with attenuated eGFR decline during follow-up.

Dr. Katherine Tuttle of the University of Washington School of Medicine in Seattle, the author of a related editorial, commented in email to Reuters Health that the study “has firmly established SGLT2 inhibition as new standard of care for people with type 2 diabetes and CKD.”

Using albuminuria to risk stratify and follow treatment response is “indisputable,” she said, and treatment should be intensified if albuminuria occurs. With regard to using the EGFR slope, she noted, “it will be important to determine if the historical slope prior to starting a therapy predicts the future slope for assessment of therapeutic response.”

Now that the benefits of SGLT2 inhibitors have been demonstrated, she added, “more education, coordination, and multidisciplinary/multispecialty care models are needed, as the number of patients who have an indication for CKD monitoring (albuminuria/eGFR) and treatment with SGLT2 inhibitors is enormous. Optimal care will clearly require team efforts.”

The study was funded by Astra Zeneca. Dr. Heerspink and most of the coauthors have received funds from the company, as has Dr. Tuttle.

SOURCE: https://bit.ly/3ppM4CJ and https://bit.ly/3plMABP Lancet Diabetes and Endocrinology, online October 4, 2021.

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