Conditions: Diabetes Mellitus, Non-Insulin-Dependent
Keywords: Impaired Fasting Glucose (IFG) Impaired Glucose Tolerance (IGT)
Allocation: RANDOMIZED | Intervention model: FACTORIAL
Enrollment: 12537
Healthy volunteers: no

Brief summary:
The primary objectives of the ORIGIN study were:

* To determine whether insulin glargine-mediated normoglycemia can reduce cardiovascular morbidity and/or mortality in people at high risk for vascular disease with either Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or early type 2 diabetes;
* To determine whether omega-3 fatty acids can reduce cardiovascular mortality in people with IFG, IGT or early type 2 diabetes.

The secondary objectives of the insulin glargine study were to determine if insulin glargine-mediated normoglycemia can reduce:

* total mortality (all causes);
* the risk of diabetic microvascular outcomes;
* the rate of progression of IGT or IFG to type 2 diabetes.

Detailed description:
The ORIGIN study was conducted by the Population Health Research Institute in Hamilton, Ontario (Canada), working in conjunction with the sponsor, and an independent Steering Committee.

Routine visits were to occur at 2, 4, 8, and 16 weeks following randomization, then every four months for the rest of the study, for all participants

The duration of the study was based on the number of events observed (event-driven study) and was originally planned to be 5 years. In 2008-2009 ORIGIN's follow-up was extended by approximately 2 years, because of published literature of completed studies suggesting that a longer period of effective glycemic contrast between treatments might be needed to see an effect on cardiovascular events.

Arms:
arm 1: * Insulin glargine once daily by subcutaneous injection in a titrated regimen targeting a fasting plasma glucose (FPG) level of ≤95 mg/dL (5.3 mmol/L)
* One capsule of omega-3 polyunsaturated fatty acids once daily arm 2: * Insulin glargine once daily by subcutaneous injection in a titrated regimen targeting a fasting plasma glucose (FPG) level of ≤95 mg/dL (5.3 mmol/L)
* One capsule of placebo once daily arm 3: • One capsule of omega-3 polyunsaturated fatty acids once daily arm 4: • One capsule of placebo once daily

Interventions: intervention 1: insulin glargine (HOE901) intervention 2: omega-3 polyunsaturated fatty acids (PUFA) intervention 3: placebo intervention 4: reusable pen device for insulin injection
Intervention descriptions: intervention 1: Cartridges for use in a pen device, each containing 3 mL of insulin glargine 100 U/mL solution for injection intervention 2: Gelatin capsules (containing icosapent ethyl esters 465 mg and doconexent ethyl esters 375 mg) for oral administration intervention 3: Matching placebo gelatin capsules (containing olive oil) for oral administration intervention 4: None

Protocol document: