The EMPA-REG OUTCOME trial shows short- and long-term benefits of empagliflozin on albuminuria in patients with T2D and CVD.
An analysis of the EMPA-REG OUTCOME trial has revealed short- and long-term benefits of empagliflozin on albuminuria in 6953 patients with type 2 diabetes (T2D) and cardiovascular disease (CVD).
A sodium-glucose co-transporter-2 (SGLT2), empagliflozin was studied in a randomized, double-blind, placebo-controlled trial at 590 sites in 42 countries. Patients with T2D and established CVD who were 18 years of age and older were assigned 1:1:1 to empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care.
The patients in the study were enrolled between September 2010 and April 2013, when 7028 patients were randomly assigned to treatment groups; 7020 patients received treatment and baseline data was collected on 6953 patients. Of these patients, 4171 had normoalbuminuria (2789 were assigned to empagliflozin), 2013 had microalbuminuria (1338 were assigned to empagliflozin), and 769 had macroalbuminuria (509 were assigned to empagliflozin).
The study was conducted until at least 691 patients experienced an adjudicated event in the primary outcome; the median treatment duration was 2.6 years and median observation time was 3.1 years.
In the short term, at week 12, the placebo-adjusted mean ratio of urinary albumin-to-creatinine change in patients with normoalbuminuria from baseline was -7% (95% Confidence Interval [CI], -12 to -2; P = .013). In patients with microalbuminuria the mean change from baseline was -25% (95% CI, -31 to -19; P < .0001) and in patients with macroalbuminuria the mean change was -32% (95% CI, -4 to -23; P < .0001). These reductions were maintained in all 3 groups compared with placebo over the long term, as measured at week 164.
After treatment ceased for a median of 34 or 35 days, reductions in urinary albumin-to-creatinine ratios were -22% in the empagliflozin group compared with the placebo group for the patients with microalbuminuria (95% CI, -32 to -11; P = .0003) and -29% for the patients with macroalbuminuria (95% CI, -44 to -10; P = .0048). However, there was no reduction in urinary albumin-to-creatinine ratios in the patients with normoalbuminuria, with a 1% increase in rate (95% CI, -8 to 10; P = .8911).
“These results support short-term and long-term benefits of empagliflozin on urinary albumin excretion, irrespective of patients' albuminuria status at baseline.” the researchers, led by David ZI Cherney, MD, of the Department of Medicine and Department of Physiology, Division of Nephrology, University Health Network, University of Toronto and Toronto General Hospital, wrote.
The study also found that patients treated with empagliflozin were more likely to show sustained improvement from microalbuminuria to normoalbuminuria and from macroalbuminuria to microalbuminuria or normoalbuminuria. They were also less likely to show deterioration from normoalbuminuria to microalbuminuria or macroalbuminuria.
The proportion of patients receiving empagliflozin who experienced any adverse events (AEs), serious AEs, or AEs that led to discontinuing the study increased with respective worsening of urinary albumin-to-creatinine ratios at baseline, but these rates were similar between the treatment groups.
The study was published in The Lancet Diabetes & Endo.