A Meta-Analysis of Amputation Risk in Empagliflozin Studies (1245.25, 1245.110, 1245.121)

1245-0171

The primary objective of this exploratory meta-analysis is to evaluate the frequencies, incidence rates, and hazard ratios of lower-limb amputation (LLA) events (primary outcome) and of adverse events related to amputation (secondary outcome) in patients treated with empagliflozin compared with placebo in the pooled population of the long-term studies 1245.25, 1245.110, and 1245.121 (SAF-M1), in the pooled population of studies 1245.110 and 1245.121 (SAFM2), and in each of the 3 studies separately.

2021-06-01

2021-07-13

2021-07-13

Completed

16746

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

{'studyType': 'OBSERVATIONAL', 'patientRegistry': False, 'designInfo': {'observationalModel': 'OTHER', 'timePerspective': 'RETROSPECTIVE'}, 'enrollmentInfo': {'count': 16746, 'type': 'ACTUAL'}}

2024-02-08