This Study Combines Data From 3 Other Studies Testing Empagliflozin in Patients With Diabetes or With Chronic Heart Failure. The Study Looks at the Numbers of Patients Who Had Lower Limb Amputations

Inclusion criteria

for 1245.25:

• Age ≥18 years, diagnosis of type 2 diabetes mellitus (T2DM)
• Drug-naïve or pretreated with any background therapy
• Glycated haemoglobin (HbA1c) criteria

• Patients who were drug-naïve: HbA1c of 7 to 10%
• Patients with background therapy: HbA1c of 7 to 9%
• Body mass index (BMI) ≤45 kg/m2
• With high cardiovascular risk, defined as ≥1 of the following criteria

• History of myocardial infarction (>2 months prior to enrollment)
• Multi-vessel coronary artery disease: ≥2 major vessels or left main coronary artery
• Single-vessel coronary artery disease with no scheduled revascularization/previously unsuccessful revascularization
• Hospital discharge due to unstable angina pectoris (>2 months prior to enrollment)
• History of stroke (>2 months prior to enrollment)
• Peripheral occlusive arterial disease

Inclusion criteria

for 1245.110 and 1245.121

• Age ≥18 years (Japan, age ≥20 years)
• Chronic heart failure (HF) new york hear association (NYHA) class II to IV
• Ejection fraction (EF) and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) criteria

• 1245.110: preserved EF (Left ventricular ejection fraction (LVEF) >40%) and elevated NT-proBNP (>300 pg/ml; >900 pg/ml for patients with atrial fibrillation)
• 1245.121: reduced EF (LVEF ≤40%) and elevated NT-proBNP (≥2500 pg/ml if EF 36 to 40%, ≥1000 pg/ml if EF 31 to 35%, ≥600 pg/ml if EF ≤30% or if EF ≤40% with documented hospitalisation for HF within 12 months prior to screening; for patients with atrial fibrillation, double the level of NT-proBNP is applied for each EF category)
• 1245.110 only: structural heart disease within 6 months or documented hospitalisation for HF within 12 months prior to screening
• 1245.121 only: stable dose of medical therapy for HF consistent with local and international cardiology guidelines

Exclusion criteria

for 1245.25

• Uncontrolled hyperglycemia: fasting plasma glucose >240 mg/dl
• Severe renal impairment defined as eGFR <30 ml/min by Modification of diet in renal disease (MDRD) formula
• Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial, or participating in another trial (involving an investigational drug and/or follow-up)

Exclusion criteria

for 1245.110 and 1245.121

• Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or transient ischaemic attack ≤90 days before screening
• Heart transplant recipient, or listed for heart transplant
• Acute decompensated HF
• Systolic blood pressure (SBP) ≥180 mmHg at randomisation
• Symptomatic hypotension and/or SBP <100 mmHg at screening or randomisation
• Impaired renal function defined as Estimated glomerular filtration rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration Equation (based on serum creatinine value) <20 ml/min/1.73 m2 or requiring dialysis at screening