medwireNews: Dapagliflozin slows the long-term decline in estimated glomerular filtration rate (eGFR), and reduces albuminuria, particularly in people with type 2 diabetes, report the DAPA-CKD investigators.
Hiddo Heerspink (University Medical Centre Groningen, the Netherlands) and colleagues have published the findings in two papers in The Lancet Diabetes & Endocrinology.
In a linked commentary, Katherine Tuttle (University of Washington School of Medicine, Seattle, USA) highlights the importance of the eGFR decline analysis, “since the field is moving towards eGFR slope as a potential outcome for clinical trials, especially for interventions at earlier stages of chronic kidney disease, when occurrence of clinical kidney disease events as endpoints is less feasible.”
The researchers found that being assigned to dapagliflozin treatment (n=2152) was associated with having an average 24.8% slower eGFR decline versus use of placebo (n=2152) between baseline and the end of follow-up (median 2.3 years). The average annual rates of decline, which included the early acute reductions in participants taking dapagliflozin, were 2.88 versus 3.83 mL/min per 1.73 m2, respectively.
The effect of dapagliflozin was significantly larger in people with type 2 diabetes than those without, at an average difference versus placebo of 29.2% and 12.6%, respectively, or of 1.18 versus 0.46 mL/min per 1.73 m2 annually.
The eGFR decline was larger among participants with higher baseline glycated hemoglobin (HbA1c); however, the benefit of dapagliflozin was also significantly greater in these people. The treatment benefit was also significantly greater in people with diabetic nephropathy as their underlying cause of kidney disease, at an average difference in eGFR versus placebo of 30.9% compared with 11.1–18.3% for other causes.
Finally, the researchers found that eGFR declined significantly faster in people in the highest two urinary albumin-to-creatinine ratio (UACR) subgroups, but that these people derived significantly greater attenuation of eGFR decline with dapagliflozin treatment than those in the lowest two subgroups.
In line with this, the UACR analysis showed that larger improvements in this measure were associated with greater attenuation of eGFR decline.
Overall, people taking dapagliflozin versus placebo achieved an average 26.5% reduction in UACR by week 2, and this was sustained for the duration of the trial.
Again, the effect was significantly greater in people with than without diabetes, at average reductions of 35.1% versus 14.8%. Although median baseline UACR was higher in people with than without diabetes (1017 vs 861 mg/g), this did not account for the difference in treatment effect, say the researchers.
As with eGFR, the effect of dapagliflozin was significantly greater in people with underlying diabetic nephropathy, at 36.6% versus 13.6–21.3% for other causes, and the effect increased with higher HbA1c.
Finally, dapagliflozin treatment significantly reduced the risk for albuminuria progression and increased the likelihood for regression, with the latter effect strongest in people with type 2 diabetes.
In her commentary, Tuttle concludes: “[N]ow that the evidence is clear for the lifesaving and health-preserving benefits of new chronic kidney disease therapies, the health-care community must squarely focus on dissemination and implementation to provide therapeutic access to the enormous number of people worldwide who stand to benefit.”
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Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00242-4
Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00243-6
Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00265-5