Insulin Use Early in the Course of Type 2 Diabetes Mellitus: The ORIGIN Trial

There has been a recent shift from a uniform treatment targeting HbA1c to a patient centered approach due to disappointing results of intensified glucose control in mega-trials such as VADT, ADVANCE, and ACCORD. In addition, morbidity and mortality has been substantially reduced since the UKPDS leading to an overestimation of the absolute risk for cardiovascular complications in randomized controlled trials. With substantial progress in prevention of cardiovascular complications, patients with type 2 diabetes now survive long enough to face diabetes-related complications and cancer risk. This requires rethinking of antidiabetic treatment strategies as exemplified by a recent consensus statement of the EASD and ADA, calling for a more patient centered treatment. Within this context the value of early insulin initiation was reinforced, the clinical utility of which has been demonstrated in the recent ORIGIN trial. ORIGIN demonstrated neutral results for the primary endpoint, but reduced microangiopathy in patients with an HbA1c value of ≥6.4 % with basal insulin glargine. After 5 years of follow-up 77 % of the patients in the glargine arm and 66 % with standard care remained at an HbA1c <7 %. An ongoing long-term follow-up (ORIGINALE) will clarify whether this also translates into a reduction of macrovascular events and mortality.