Dapagliflozin Cuts Risk of Diabetes in Patients with Chronic Kidney Disease

One year after an analysis of DAPA-HF found use of dapagliflozin (Farxiga) reduced the onset of diabetes by 32% in patients with heart failure, new research from DAPA-CKD suggests use was associated with a 38% reduction in new onset diabetes among those with chronic kidney disease (CKD) from the phase 3 trial.

While investigators noted failure to reach statistical significance, they purport results still provide evidence linking use of dapagliflozin to a decrease in the incidence of the type 2 diabetes among patients seen in either phase 3 trial.

“In this nondiabetic population with chronic kidney disease of different types, we looked into the progression to diabetes during the duration of the trial and we saw approximately a 30% reduction in progression. It was of the exact same magnitude of the reduction of progression to diabetes as was seen in the DAPA-HF study,” said Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at the Steno Diabetes Center, in an interview with Endocrinology Network.

With a DAPA-HF analysis presented at the previous year’s conference, the ADA 2021 analysis was designed with the intent of assessing how use of dapagliflozin might influence rate of new-onset diabetes in patients with CKD. A prespecified exploratory analysis, the current study assessed a subgroup of 1398 patients with no prior history of diabetes and an HbA1c less than 6.5% at baseline.

During a follow-up period lasting a median of 2.4 years, 4.7% (33 of 701) of the placebo group and 3.0% (21 of 697) of the dapagliflozin group, which investigators pointed out responded to event rates of 2.4 per 100-patient years in the placebo group and 1.5 per 100-patient years in the dapagliflozin group. Results of the investigators’ analyses indicated dapagliflozin was associated with a 38% reduction in risk of developing type 2 diabetes (HR, 0.62; 95% CI, 0.36-1.08).

No heterogeneity was observed in regard to the effect of dapagliflozin on diabetes prevention based on most subgroups, including those based on age, glycemic status, blood pressure, eGFR, and other factors. However, investigators noted the effect was more pronounced in female patients (P for interaction=.03). Of those who went on to develop diabetes during the trial, 90% had prediabetes at baseline.

In a meta-analysis coming data from DAPA-CKD and DAPA-HF, results suggested dapagliflozin was associated with a 34% reduction in new-onset diabetes (HR, 0.66; 95% CI, 0.51-0.87; P=.003), without heterogeneity between studies (P for interaction=0.78).

“In these groups of people where you have a high risk for cardiovascular disease, kidney disease, and metabolic complications, you can prevent diabetes or at least delay diabetes,” added Rossing.

For more on the results of this study and the implications for dapagliflozin use as clinicians and researchers push for greater uptake in primary care settings, check out our ADA 2021 House Call with Rossing.

This study, “Dapagliflozin and the Incidence of Type 2 Diabetes in Patients with Chronic Kidney Disease,” was presented at ADA 2021.