Title: Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial
Cherney, DZ et al.
What You Need to Know:
According to results pooled from short-term trials, treatment with empagliflozin, a sodium-glucose co-transporter-2 inhibitor, has both short-term as well as long-term benefits on urinary albumin excretion in patients with type 2 diabetes and known cardiovascular disease.
- Double-blind, placebo-controlled exploratory analysis of the EMPA-REG OUTCOME study evaluated the effects of empagliflozin on albuminuria in type 2 diabetic patients and established cardiovascular disease
- 7028 patients were randomized (1:1:1) to receive 10mg empagliflozin, 25mg empagliflozin, or placebo, in addition to standard of care treatment, until ≥691 patients experienced a primary outcome event
- Primary endpoint: percent of patients who achieved a ≥50% American College of Rheumatology response (ACR50) at month 6 (analyzed in all patients who received ≥1 dose of study treatment)
- In this analysis, data reported was the pooled urinary albumin-to-creatinine ratio (UACR) in the empagliflozin group versus placebo group according to baseline albuminuria status
- 7020 patients received treatment
- Baseline UACR data (n=6953) patients: 4171 patients had normoalbuminuria (59% of treated patients; 1382 placebo patients, 2789 empagliflozin patients), 2013 patients had microalbuminuria (29% of treated patients; 675 placebo patients, 1338 empagliflozin patients), and 769 patients had macroalbuminuria (11% of treated patients; 260 placebo patients, 509 empagliflozin patients)
- “After short-term treatment at week 12, the placebo-adjusted geometric mean ratio of UACR change from baseline with empagliflozin was −7% (95% CI −12 to −2; p=0·013) in patients with normoalbuminuria, −25% (−31 to −19; p<0·0001) in patients with microalbuminuria, and −32% (−41 to −23; p<0·0001) in patients with macroalbuminuria”
- At week 164, UACR reductions were maintained for all groups vs placebo
- Placebo-corrected geometric mean ratio of relative change in UACR from baseline in patients treated with empagliflozin 34-35 days after treatment cessation: -22% for patients with baseline microalbuminuria (95% CI: -32, -11; P=0.0003) -29% for patients with baseline macroalbuminuria (95% CI: -44, -10; P=0.0048), and 1% for patients with baseline normoalbuminuria (95% CI: -8, 10; P=0.8911)
- Patients treated with empagliflozin were more likely to experience a sustained improvement from microalbuminuria to normoalbuminuria (hazard ratio [HR] 1·43, 95% CI 1·22 to 1·67; p<0·0001) or from macroalbuminuria to microalbuminuria or normoalbuminuria (HR 1·82, 1·40 to 2·37; p<0·0001), and less likely to experience a sustained deterioration from normoalbuminuria to microalbuminuria or macroalbuminuria (HR 0·84, 0·74 to 0·95; p=0·0077)
- Similar rate of adverse events, serious adverse events, and adverse events causing treatment discontinuation between groups; rates were increased in patients with worsening baseline UACR status
- Higher rate of genital infections was seen in empagliflozin patients vs placebo patients