Advancing therapy in type 2 diabetes mellitus with early, comprehensive progression from oral agents to insulin therapy

Early and intensive glycemic control is necessary to prevent or minimize the development of microvascular and macrovascular complications in individuals with type 2 diabetes mellitus. However, many patients are unable to attain glycemic control, partly due to protracted treatment with oral antidiabetic drugs (OADs) despite inadequate control and barriers to initiating insulin therapy. Patients at different stages of disease may benefit from the early introduction of intensive glycemic control.

This article discusses some of the potential barriers to achieving and maintaining optimal glycemic levels in patients whose blood glucose is sub-optimally controlled with OADs and reviews the benefits of early introduction of intensive glycemic control in patients at various stages of disease, with an emphasis on insulin therapy.

Relevant English-language articles published from 1996 to 2006 were identified through searches of the National Center for Biotechnology PubMed database. Search terms included insulin, insulin therapy, type 2 diabetes, insulin analogs, early insulinization, and diabetes prevention, among others. Studies were assessed regarding designs, primary and secondary efficacy parameters, glycosylated hemoglobin (HbAM(lc)), fasting plasma glucose, incidence of hypoglycemia, and other safety assessments. Inclusion criteria were multicenter, randomized, open-label, parallel-group trials, as well as retrospective observational studies, conducted in Europe or the United States. Additional analyses and guideline-based recommendations are included.

The landmark results of the United Kingdom Prospective Diabetes Study, which found that an intensive strategy in 3867 newly diagnosed patients with type 2 diabetes was associated with stricter glycemic control than was conventional care (HbA(lc) over 10 years, 7.0% vs 7.9%; P < 0.001), as well as a 25% reduction in the risk for microvascular complications (P = 0.01). Early initiation of insulin therapy concomitantly with OADs appeared well tolerated in the populations studied, was effective in recently diagnosed patients, and may also confer anti-inflammatory and antiatherogenic effects. Characteristics associated with newer formulations of insulin (eg, basal insulin analogues as well as rapid-acting insulin analogues, the insulin pump, or inhaled insulin) may help overcome barriers associated with initiating insulin therapy.

Based on the literature, early and persistent intensification of antidiabetic therapy is an approach that most likely will achieve optimal glycemic control in patients with type 2 diabetes and help prevent associated complications. Greater clinical experience with newer therapeutic approaches, including incretin mimetics and dipeptidyl peptidase-IV inhibitors, will provide insight into their place in the spectrum of diabetes treatments.