Defining the Role of Insulin Lispro in the Management of Postprandial Hyperglycaemia in Patients with Type 2 Diabetes Mellitus

The role of postprandial hyperglycaemia in contributing to the risk of both micro- and macrovascular complications in patients with diabetes mellitus is being increasingly recognized. In type 2 diabetes, there is a progressive shift in the relative contributions of postprandial and fasting hyperglycaemia to the overall glycaemic control as the disease progresses. For patients with fairly good glycaemic control (glycosylated haemoglobin [HbA_1c] <8.5%), postprandial hyperglycaemia makes a relatively greater contribution to the overall glycaemic load than fasting hyperglycaemia, but in patients with poorer control, the relative contribution of the two states to the overall glycaemic load is reversed. This finding, coupled with epidemiological evidence that elevated postprandial glucose concentration is an independent risk factor for cardiovascular disease (CVD), and is associated with a greater CVD risk than elevated fasting glucose, points to the need to monitor and target postprandial glucose, as well as fasting glucose and HbA_1c levels, when optimizing insulin therapy for patients with type 2 diabetes. When insulin therapy becomes necessary in patients with type 2 diabetes who can no longer be controlled with oral antihyperglycaemic therapy, use of short-acting insulin analogues with a rapid onset of action and capable of controlling postprandial glycaemic excursions when injected immediately before a meal, has advantages over regular human insulin in that they provide a more favourable time-action profile that mimics normal physiological insulin secretion. Among the available rapid-acting insulin analogues, insulin lispro has been shown to reduce postprandial glucose concentrations to a significantly greater degree than regular human insulin in patients with type 2 diabetes. Moreover, premixed combinations of insulin lispro with the longer acting analogue neutral insulin lispro protamine suspension in 25% : 75% or 50% : 50% combinations are significantly more effective in lowering postprandial blood glucose concentrations than premixed regular human insulin plus neutral protamine Hagedorn (NPH) 30% : 70%. The premixed insulin lispro combinations offer the advantage of fewer daily injections than intensive insulin therapy, and the convenience of not having to mix insulin preparations manually. Although it has yet to be conclusively established that targeting postprandial hyperglycaemia reduces CVD risk, the potential benefits of improved postprandial and interprandial hyperglycaemia favour the use of newer insulin analogues, such as insulin lispro and insulin lispro mixes, over conventional insulin therapy, whenever insulin therapy becomes necessary in patients with type 2 diabetes.