ADA 2021: Use of Dapagliflozin Decreases Risk of Diabetes in Patients with CKD

A prespecified analysis of the Dapagliflozin in Patients with Chronic Kidney Disease (DAPA-CKD) trial found use of dapagliflozin (Farxiga®, AstraZeneca) led to a 38% reduction in type 2 diabetes (T2D) incidence among participants with chronic kidney disease (CKD).

The new findings were presented at the American Diabetes Association 81st Scientific Sessions (ADA 2021), held virtually between June 25-29, 2021.

The DAPA-CKD trial was the first dedicated CKD trial of the sodium-glucose cotransporter-2 inhibitor that included patients both with and without T2D and to specify renal outcomes as the primary endpoint.

In the current analysis, researchers from the DAPA-CKD study group examined the effect of dapagliflozin on incident T2D in a cohort of patients enrolled in DAPA-CKD without T2D. This included 1398 patients with CKD, no prior history of diabetes, and A1c <6.5% at baseline.

Surveillance for new-onset T2D (A1c ≥6.5%) was accomplished through periodic A1c testing and comparison between treatment groups assessed through Cox proportional hazards model.

Researchers found over a median follow-up of 2.4 years, T2D developed in 4.7% (33/707) of participants in the placebo group and 3% (21/697) of participants in the dapagliflozin group. This corresponded to event rates of 2.4/100-patient years and 1.5/100-patient years, respectively.

As previously mentioned, use of dapagliflozin led to a 38% reduction in T2D incidence (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.36-1.08). More than 90% of the participants who developed T2D had prediabetes at baseline (A1c, 5.7%-6.4%).

There was no heterogeneity in the effect of dapagliflozin on T2D prevention based on most key prespecified subgroups, including age, glycemic status, blood pressure, estimated glomerular filtration rate, albuminuria, race, and region; however, the effect was more pronounced in women (p _interaction =0.03).

Data from a meta-analysis of DAPA-CKD and the DAPA-HF (dapagliflozin in heart failure with reduced ejection fraction) trial, demonstrated that dapagliflozin reduced new-onset diabetes compared to placebo (HR, 0.66; 95% CI, 0.51-0.87; p=0.003), without heterogeneity between studies (p _interaction =0.78), according to study authors.

“In this pre-specified explorative analysis of patients with CKD, treatment with dapagliflozin reduced the incidence of new T2D, an effect that was consistent across DAPA-CKD and DAPA-HF,” concluded authors.

Reference: Rossing P, Vart P, Chertow GM, et al. Dapagliflozin and the incidence of type 2 diabetes in patients with chronic kidney disease. American Diabetes Association Presented Friday, June 25, 2021, 130-LB—2021.

For a Patient Care Online conversation with DAPA-CKD principal investigator John McMurray, Professor of Cardiology at the University of Glasgow Institute of Cardiovascular and Medical Sciences, please click here.

The original study, Dapagliflozin in patients with chronic kidney disease, was published in October 2020 in The New England Journal of Medicine.