Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes.

The natural history of type 2 diabetes mellitus (T2DM) is a relentless progression of β-cell failure and dysregulation of β-cell function with increasing metabolic derangement. Insulin remains the only glucose-lowering therapy that is efficacious throughout this continuum. However, the timing of introduction and the choice of insulin therapy remain contentious because of the heterogeneity of T2DM and the well-recognized behavioral and therapeutic challenges associated with this mode of therapy. Nevertheless, the early initiation of basal insulin has been shown to improve glycemic control and affect long-term outcomes in people with T2DM and is a treatment strategy supported by international guidelines as part of an individualized approach to chronic disease management. The rationale for early initiation of insulin is based on evidence demonstrating multifaceted benefits, including overcoming the glucotoxic effects of hyperglycemia, thereby facilitating "β-cell rest," and preserving β-cell mass and function, while also improving insulin sensitivity. Independent of its effects on glycemic control, insulin possesses anti-inflammatory and antioxidant properties that may help protect against endothelial dysfunction and damage resulting in vascular disease. Insulin therapy and the achievement of good glycemic control earlier in T2DM provide long-term protection to end organs via "metabolic memory" regardless of subsequent treatments and degree of glycemic control. This is evidenced from long-term observations continuing from trials such as the United Kingdom Prospective Diabetes Study. As such, early initiation of insulin therapy may not only help to avoid the effects of prolonged glycemic burden, but may also positively alter the course of disease progression.