Use of insulin in type 2 diabetes: What we learned from recent clinical trials on the benefits of early insulin initiation

The majority of people with type 2 diabetes mellitus (T2DM) require insulin therapy to maintain HbA_1c levels < 7% during the first decade of diagnosis. Large prospective trials investigating the cardiovascular (CV) benefits of intensive glycaemic control have produced inconsistent results; however, meta-analyses have suggested that intensive glycaemic control provides both micro- and macrovascular benefits. The ORIGIN study investigated the impact of basal insulin glargine therapy targeting ≤ 5.3 mmol/L for fasting plasma glucose compared with standard care on CV outcomes in people with pre- or early diabetes, and demonstrated a neutral effect on CV outcomes with long-term use of insulin glargine early in the course of diabetes, with a low rate of severe hypoglycaemia and modest weight gain. The EARLY, GLORY and EASIE studies also demonstrated that insulin use earlier in the treatment pathway led to improved glycaemic control, reduced weight gain and fewer hypoglycaemic episodes than when insulin was added later in the course of disease. The beneficial effect of early transient intensive insulin therapy (TIIT) at diagnosis has been demonstrated in a number of trials; it rapidly limits the damage caused by gluco- and lipotoxicity, improving residual β-cell function and potentially slowing disease progression. The evidence suggests that people newly diagnosed with T2DM and HbA_1c > 9% should be given early TIIT to achieve normoglycaemia within weeks, after which standard care should then be adopted. Insulin use earlier in the treatment pathway should be considered, as it reduces the risk of hypoglycaemia as well as allows β-cell rest, which can help preserve β-cell function.