麻豆传媒

In patients with type 2 diabetes and chronic kidney disease, empagliflozin (Jardiance) slowed renal decline, reported in a slope analysis of the l.

Lead author , of the University Hospital of Würzburg in Germany, and colleagues reported improved estimated glomerular filtration rate (eGFR) levels. During the first 4 weeks of intervention, patients experienced an initial drop in eGFR compared to a small gain in the placebo group. In a 2.5 year "chronic period," the empagliflozin group exhibited stabilization of kidney function compared with the natural progression of kidney function among the placebo group (mean decline of 2 mL/min/1.73 m2 per year).

The goal of the slope analysis was to "assess treatment differences in the rate of change in estimated GFR over time in the trial using random intercept, random coefficient linear regression models yielding mean and individual slopes of estimated GFR," the authors explained in their presentation at the American Society of Nephrology's Kidney Week meeting.

After cessation of treatment among the intervention group, patients with diabetic kidney disease trended back towards baseline eGFR levels. "You get back the price you paid at the beginning," Wanner explained, adding that, on average, participants gained approximately 0.56 mL/min per week back.

Co-author , of Yale School of Medicine in New Haven, Conn., explained to 麻豆传媒 that the group has been successful at identifying some of the cardiovascular benefits of empagliflozin in previous analyses of the, citing reduced CV mortality and heart failure hospitalizations. Empagliflozin was associated with reduced rates of worsening nephropathy during the chronic phase (12.7% of patients versus 18.8% placebo, hazard ratio 0.61, 95% CI 0.53-0.70, P<0.001). There also was a near doubling of serum creatinine levels among the placebo group (relative risk reduction 44%, 1.5% versus 2.6%).

Inzucchi explained they were pleased with the findings of the current slope analysis, which was successful at identifying the renal benefits of empagliflozin, a SGLT2 inhibitor. "There has not been a new treatment for diabetic kidney disease since the ACE inhibitors and ARBs many years ago," he noted. "Our data suggests that there may be a new option to curtail the worsening of kidney disease in patients with diabetes. This is very exciting and has major implications not only for patients' health but also for societal healthcare costs."

Among the 7,020 participants, eGFR at baseline was approximately 74 mL/min, while 1,800 had chronic kidney disease (CKD) defined by an eGFR of less than 60 mL/min. They were randomized into three groups: 10 mg of empagliflozin, 25 mg, or a placebo.

In addition to diabetic kidney disease, the researchers also examined slopes in the trial cohort with macroalbuminuria at baseline, which was 11% of the trial population (n=700). Using the adjusted eGFR mean values, patients with macroalbuminuria experienced similar trends after starting empagliflozin. During the chronic phase of treatment, the empagliflozin group's eGFR levels stabilized, compared with the placebo group, who grew closer toward macroalbuminuria, with an average change of 12 mL/min/1.73 m2 between groups.

, of University of California Irvine Health, told 麻豆传媒 that "previous findings from the trial have shown that receipt of the anti-diabetic drug, empagliflozin ... led to reduced rates of cardiovascular events and death, as well as reduced CKD progression."

Rhee, who was not involved in the current study, noted that "there are a growing number of medications in the armamentarium of treating type 2 diabetes, [but] there remain major knowledge gaps with respect to the efficacy and safety of these agents in the context of CKD. Thus, these findings add important new knowledge regarding the potential benefits of empagliflozin upon the health and survival of diabetic kidney disease patients with high underlying cardiovascular risk."

Inzucchi said his group plans to continue analysis of the EMPA-REG data to determine which subgroups benefited the most and the least from treatment. Future analyses should also identify "what the mediators of this renal benefit might have been." He suggested it could be glucose, blood pressure, or something else entirely, such as "an intrinsic effect of SGLT2 inhibition or of empagliflozin itself."

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