Efficacy and safety of empagliflozin in older patients in the EMPA-REG OUTCOME® trial.

OBJECTIVE: The risks of cardio-renal complications of diabetes increase with age. In the EMPA-REG OUTCOME® trial, empagliflozin reduced cardiovascular (CV) mortality by 38% in patients with type 2 diabetes (T2D) and CV disease. Here we compare outcomes with empagliflozin in older patients in EMPA-REG OUTCOME. METHODS: Patients with T2D and CV disease were randomised to empagliflozin 10 or 25 mg, or placebo plus standard of care. In post hoc analyses, risks of 3-point major adverse CV events (3P-MACE: composite of CV death, non-fatal myocardial infarction (MI) or non-fatal stroke), CV death, hospitalisation for heart failure, all-cause mortality, all-cause hospitalisation and incident/worsening nephropathy were evaluated for empagliflozin versus placebo by baseline age (<65, 65 to <75, ≥75 years). Adverse events (AEs) were analysed descriptively. RESULTS: Effect of empagliflozin on all outcomes was consistent across age categories (P ≥ 0.05 for interactions) except 3P-MACE. The 3P-MACE hazard ratios (HRs) were 1.04 (95% confidence interval [CI] 0.84, 1.29), 0.74 (0.58, 0.93) and 0.68 (0.46, 1.00) in patients aged <65, 65 to <75, and ≥75 years, respectively (P = 0.047 for treatment-by-age group interaction). Corresponding CV death HRs were 0.72 (95% CI 0.52, 1.01), 0.54 (0.37, 0.79) and 0.55 (0.32, 0.94), respectively (P = 0.484 for treatment-by-age group interaction). Across age categories, empagliflozin AEs reflected its known safety profile. Rates of bone fractures, renal AEs and diabetic ketoacidosis were similar between empagliflozin and placebo across age categories. CONCLUSIONS: In the EMPA-REG OUTCOME trial, empagliflozin reduced risks of CV mortality, heart failure and renal outcomes, supporting its cardio-renal benefits in older patients.

Empagliflozin in combination with oral agents in young and overweight/obese Type 2 diabetes mellitus patients: A pooled analysis of three randomized trials.

AIMS: This analysis aimed to evaluate efficacy and safety of empagliflozin in combination therapy in <65 y.o. patients, overweight/obese, and with uncontrolled T2DM. METHODS: Pooled analysis from three phase-III trials, in <65 y.o. patients, with BMI 25-35kg/m2, and HbA1c ≥8% at baseline. Patients (N=439) were randomized to placebo (n=138), empagliflozin 10mg (n=160), or empagliflozin 25mg (n=141) once daily (24weeks) as add-on to metformin, to metformin plus sulfonylurea, or to pioglitazone ± metformin. RESULTS: At week 24, adjusted mean (SE) changes from baseline in HbA1c were -0.19% (0.07) for placebo vs. -1.10% (0.07) and -1.10% (0.07) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adjusted mean (SE) changes from baseline in weight were -0.33kg (0.21) for placebo vs. -1.94kg (0.19) and -2.14kg (0.20) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adverse events were reported in 57.2% on placebo, 64.4% on empagliflozin 10mg and 59.6% on empagliflozin 25mg. Genital infection AEs were reported in 1.4% on placebo, 3.8% on empagliflozin 10mg, and 5.0% on empagliflozin 25mg. CONCLUSIONS: In this specific population, empagliflozin in combination with other oral agents, significantly reduced HbA1c and body weight and was well tolerated.