Study Outline

This multicenter open-label, randomized, parallel-group trial examined the efficacy of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes. A detailed outline of the trial was described previously (26, 27), but in brief, a total of 2542 patients with type 2 diabetes, with hypertension and/or dyslipidemia, were registered at 81 clinical sites in Japan. The patients were randomly assigned at a 1:1 ratio to either conventional therapy for treatment targets of HbA1c, blood pressure, and lipids (HbA1c <6.9%, blood pressure <130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol <120mg/dL), specified in the Japanese guideline (29), or intensive therapy for stricter treatment targets (HbA1c <6.2%, blood pressure <120/75 mm Hg, LDL-cholesterol <80 mg/dL).

Two patients were found ineligible after randomization and excluded from all the analyses, leaving a total of 2540 patients for the intention-to-treat population.

The primary outcome for the study was occurrence of any of a composite of myocardial infarction, stroke, revascularization (coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting), and all-cause mortality (26, 27).

The trial started in June 2006, and the intervention was continued until March 2016. At baseline, the mean age of the 2540 patients was 59 years, 38% of them were female, the mean duration of diabetes was 8.5 years, 54% of them had a history of smoking, and the mean HbA1c was 8.0%. These patients were followed up for a median of 8.5 years for the primary outcome (27).

This study is registered with ClinicalTrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT00300976","term_id":"NCT00300976"}}NCT00300976 (30).