Trial Outcomes & Findings for The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention) (NCT NCT00069784)

This study was conducted at 575 sites in 40 countries between August 22, 2003 and December 19, 2011. Three sites were closed and data from these sites were not analyzed following site audits and in compliance with rulings from national health authorities.

The purpose of the factorial design was to efficiently answer two independent scientifically worthwhile questions regarding insulin glargine and omega-3 fatty acids within the context of a single clinical trial. Sample size was determined based on the insulin glargine study objective. Results reported below are those of the insulin glargine study.

The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)

Number of participants with a first occurrence of one of the above events. The outcome's evaluation is based on the number of such positively-adjudicated first events occurring for patients assigned to the study groups. Assessments of the above events were reviewed by the Event Adjudication Committee who was kept blinded to the group assignment of participants. Statistical analysis is performed on the time from randomization to the first occurrence of the events. Number of participants with a composite endpoint (i.e. with first occurrence of CV death, nonfatal MI or nonfatal stroke) is provided in the first row of the statistical table.

Number of participants with a first occurrence of one of the above events (revascularization procedures included coronary artery bypass graft, percutaneous transluminal coronary angioplasty (PTCA) i.e. balloon, PTCA with stent, other percutaneous intervention, carotid angioplasty with/without stent, carotid endarterectomy, peripheral angioplasty with or without stent, peripheral vascular surgery, and limb amputation due to vascular disease). The outcome's evaluation is based on the number of such positively-adjudicated first events occurring for patients assigned to the study groups. Assessments of the above events were reviewed by the Event Adjudication Committee who was kept blinded to the group assignment of participants. Statistical analysis is performed on the time from randomization to the first occurrence of the events. Number of participants with a composite endpoint (i.e. with first occurrence of the events) is provided in the first row of the statistical table.

Number of deaths due to any cause

The composite outcome used to analyze microvascular disease progression contained components of clinical events: * the occurrence of laser surgery or vitrectomy for diabetic retinopathy (DR); * the development of blindness due to DR; * the occurrence of renal death or renal replacement therapy; as well as the following laboratory-based events: * doubling of serum creatinine; or * progression of albuminuria (from none to microalbuminuria \[at least 30 mg/g creatinine\], to macroalbuminuria \[at least 300 mg/g creatinine\]).

The incidence was determined by calculating the proportion of randomized participants without diabetes at randomization who either developed diabetes during the study or who were classified as having possible diabetes based on results of two oral glucose tolerance tests (OGTT) performed after the last follow-up visit (within 21-28 days for OGTT#1 and within 10-14 weeks for OGTT#2).

Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia, based on data recorded in the participant's diary. These were further categorized as confirmed (ie, with a concomitant home glucose reading ≤54 mg/dL \[≤3.0 mmol/L\]) or unconfirmed. Severe hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia in which the participant required the assistance of another person, and one of the following: * the event was associated with a documented self-measured or laboratory plasma glucose level ≤36 mg/dL (≤2.0 mmol/L), or * the event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.

Data on cancers that occurred in association with hospitalizations were collected systematically in both groups from the start of the study. All reported cancers occurring during the trial (new or recurrent) were adjudicated by the Event Adjudication Committee.