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.
FUNDING: Sanofi.