Initiating Insulin Therapy in Type 2 Diabetic Patients Failing on Oral Hypoglycemic Agents

T ype 2 diabetes is a chronic disease characterized by coexisting insulin deficiency and insulin resistance, with the resultant hyperglycemia leading to microand macrovascular complications. A large number of intervention trials demonstrated that improving glycemic control achieves considerable reductions of such complications (1–7). It has been estimated using the homeostasis multiple assessment (HOMA) that, at the time of diagnosis, 50% of pancreatic -cell function has been lost, with almost 4% further loss of function expected per year thereafter (8,9). Therefore, type 2 diabetes is a chronic progressive disease characterized by worsening hyperglycemia and escalating deterioration in the function of pancreatic -cells and loss of -cell mass (10). Because of the progressive nature of the disease, an evolving treatment strategy is therefore necessary to maintain both fasting and postprandial glycemic control. Recently, an American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) Consensus recommended a target of A1C 7% for good glucose control in clinical practice (11). Insulin therapy is required when dietary restrictions and lifestyle modifications combined with oral hypoglycemic agents (OHAs) failed to provide acceptable metabolic control (12). One major lesson learned from the milestone U.K. Prospective Diabetes Study (UKPDS) is the increasing requirement for multiple therapies in patients with type 2 diabetes to achieve blood glucose (BG) target control (13). The augmentation of insulin to OHAs contributed to several beneficial metabolic effects, as recently reviewed (14). However, there is ongoing debate as to whether it is more rewarding to target postprandial BG concentrations with meal-related insulin, or to target fasting BG concentrations with basal insulin. Monnier et al. (15,16) provided data to explain the relative contribution of fasting and postprandial BG to A1C in patients with mild-to-moderate hyperglycemia (A1C 7.3%) than in those with more poorly controlled blood glucose. The APOLLO trial (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetic patients failing Oral treatment), a multicenter randomized prospective study, addressed the issue of targeting either prandial or fasting BG concentrations (17).