SGLT2 inhibitor empagliflozin may have the potential to reduce the incidence of chronic renal failure in patients with type 2 diabetes in the long term, according to a post-hoc analysis of the EMPA-REG OUTCOME trial.
Among more than 7,000 patients with type 2 diabetes and established cardiovascular disease, those treated with empagliflozin (3.2%) were significantly less likely than placebo-treated patients (8.9%) to experience a decline of more than 5 ml/min/1.73m2/year in kidney function over 3 years of treatment (OR 0.327; 95% CI 0.263-0.408, P<.0001), reported Merlin C. Thomas, MBChB, PhD, of Monash University in Melbourne, Australia, at ASN Kidney Week 2017.
He noted that the finding was consistent regardless of how significant decline was defined:
More than 3.5ml/min/1.73m2 per year: OR 0.36; 95% CI 0.311-0.416; P<.0001More than 10 ml/min/1.73m2/year: OR 0.322; 95% CI 0.163-0.636; P=.0011
"Our findings suggest that empagliflozin may have the potential to protect against declining renal function and reduce the incidence of renal impairment in patients with type 2 diabetes in the long term," Thomas told MedPage Today.
"Protecting kidney function is a key aim of diabetes management. Individuals experiencing a faster decline in kidney function are not only more likely to develop end-stage renal disease, but they are also at increased risk of other complications including cardiovascular disease and heart failure," he continued.
The findings are consistent with previously reported data on the reduced rate of doubling of serum creatinine outcomes in participants treated with empagliflozin compared with placebo (1.5% versus 2.6%; OR 0.56; 95% CI 0.39-0.79), he stated during his presentation on Thursday evening.
Panel moderator Raymond R. Townsend, MD, of the University of Pennsylvania, commented that the study supports a known physiologic basis for the potential benefits of SGLT2 inhibitors.
"What was new to me was the speculative idea that we cut off GFRs, because we aren't going to get much better glucose control if you can't spill it in the urine," he told MedPage Today. "So if you have a lousy GFR, you're not going to spill that much glucose and you're not going to get that much benefit.
"But if these drugs can influence the course of kidney disease progression," he continued, "maybe that's a standalone indication and maybe they do other things besides just cause a better A1C, a little weight loss, etc."
Thomas and colleagues analyzed data on 7,020 patients with type 2 diabetes and established cardiovascular disease across 42 countries and 590 sites. All participants had an estimated glomerular filtration rate (eGFR) that was greater than 30ml/min/1.73m2.
Patients were randomized 1:1:1 receive to 10 mg of empagliflozin, 25 mg of of empagliflozin, or placebo in addition to standard of care for 3 years. EMPA-REG's main findings, first reported in 2015, were that the drug reduces the risk of adverse cardiovascular events.
The mean estimated glomerular filtration rate at baseline was 74.0 ml/min/1.73 m2 and change in decline from baseline to follow-up was calculated by utilizing linear regression models. A rapid decline in eGFR was defined by an annual decline in eGFR ≥5 ml/min/1.73m2.
Thomas concluded that the findings present an exciting opportunity to stabilize renal failure across a broad range of individuals, not just patients with type 2 diabetes and cardiovascular disease.
The EMPA-REG OUTCOME trial was funded by Boehringer Ingelheim and Eli Lilly Diabetes Alliance.
Source Reference: Thomas MC, et al "Empagliflozin (EMPA) and incidence of rapid decline in eGFR in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD): an exploratory analysis from the EMPA-REG OUTCOME trial" ASN 2017; TH-OR035.
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