When basal insulin therapy in type 2 diabetes mellitus is not enough--what next?

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by co-existing insulin deficiency (relative) and insulin insensitivity. Both fasting and post-prandial blood glucose are elevated, exposing the patient to acute and chronic complications due to micro- and macro-vascular angiopathy. Improving glycaemic control has been demonstrated to lower the risk of these complications. Owing to the progressive nature of the disease, an evolving treatment strategy is necessary to maintain glycaemic control. Insulin therapy is required when dietary and lifestyle modifications combined with oral hypoglycaemic agents fail to provide adequate glycaemic control. Adding an optimized dose of basal insulin to the existing oral therapy is a simple and widely used method for initiating insulin therapy. However, despite an effective control of fasting hyperglycaemia, further intervention to control post-prandial hyperglycaemia may become necessary to achieve HbA1c targets. Strategies for the addition of prandial insulin include administering short-acting (or rapid-acting) insulin analogues before each meal or twice-daily administration of pre-mixed insulin. As a single large meal often contributes to the greatest part of daytime hyperglycaemia, an alternative strategy is emerging with the addition of a single injection of prandial insulin prior to the meal that induces the largest post-prandial blood glucose excursion measured 2 h after the start of the meal. Over time, additional prandial boluses of insulin may be required to sustain daytime glycaemic control. This strategy offers a simple, stepwise approach to progress from basal insulin to a basal-bolus regimen. Studies are needed to validate this method and better define specific titration tactics.