A separate opinion piece questioned this finding, however, noting it derived from a subset analysis of a clinical trial that was focused on cardiac disease in diabetics, rather than from a new study focusing specifically on diabetes patients with evidence of kidney disease.
Jardiance, approved by the U.S. Food and Drug Administration in 2014, belongs to a relatively new class of sodium-glucose co-transporter-2 (SGLT2) inhibitors, called gliflozins, that work differently than older diabetes medications. Specifically, Jardiance blocks the reabsorption of glucose and sodium by the kidneys, helping to remove them through urination so as to lower their overall levels in the body.
Results of the randomized, double-blind, placebo-controlled trial,EMPA-REG OUTCOME (NCT01131676) that evaluated the treatment’s impact on cardiovascular events in diabetic patients, made investigators wonder if Jardiance could also protect kidney function in patients with diabetes and chronic kidney disease (CKD). (The original research was published the New England Journal of Medicine in November 2015, and titled, “Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.”)
According to the trial’s primary findings, Jardiance reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes who were at high risk for such events, compared to placebo. But secondary observations — regarding its effects on kidney function — intrigued investigators enough to re-evaluate that data with regard to patients with diabetes and CKD.
Their study, “Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes,” published in July (again in the New England Journal of Medicine), looked the long-term of Jardiance therapy on renal function.
Christoph Wanner, MD, and colleagues, in their subset analysis, randomly assigned patients with type 2 diabetes to receive either Jardiance, at a dose of 10 mg or 25 mg, or a placebo once daily. Pre-specified renal outcomes included incident or worsening nephropathy (kidney disease) by quantifiers of abnormal kidney function (such as excess protein excretion), initiation of renal-replacement therapy, or death from renal disease. Albuminuria — presence of albumin, which is typically found in the blood, in the urine — was also an important measure used in the study.
Results found incident or worsening nephropathy occurred in 525 of 4,124 patients (12.7%) in the treatment group and in 388 of 2,061 (18.8%) patients in the placebo group. A doubling of serum creatinine levels (a blood protein found in excessive levels in urine, a sign of kidney distress) was seen in 70 of 4,645 patients (1.5%) in the Jardiance group and 60 of 2,323 (2.6%) in the placebo group, “a significant relative risk reduction of 44%,” the researchers wrote.
Renal-replacement therapy was initiated in 13 of 4,687 patients (0.3%) in the treatment group and 14 of 2,333 placebo patients (0.6%), indicating “a lower relative risk” for such therapies in the Jardiance group.
No significant difference in the rate of incident albuminuria was observed in the two groups, and reports of adverse events were also similar.
“In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care,” the researchers concluded.
However, in an opinion piece published in Medscape, “New Data on Empagliflozin in Treating Diabetic Kidney Disease,” Tejas P. Desai, MD, points out some aspects of this study that he finds questionable. Most notably, he criticized the study for being a subset analysis, prepared for a manuscript separately from the parent EMPA-REG OUTCOME trial, and for excluding two statistical tools used to help validate clinical trial results derived from a subset of data.
“Empagliflozin may be the next efficacious drug against diabetic kidney disease,” Desai wrote in the piece. “Hopefully, the drug receives a fair shake from investigators and is studied for its effects against kidney disease in its own randomized, controlled trial and reported solely by the investigators leading the study with the appropriate statistical analyses conducted.”
Jardiance is not approved for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine).
Boehringer Ingelheim Pharmaceuticals, Inc.
Eli Lilly and Company
New England Journal of Medicine