Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials

Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing β cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual β-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk–benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes.