Pharmacological management of type 2 diabetes mellitus: rationale for rational use of insulin.

Type 2 diabetes mellitus is a chronic metabolic disorder associated with high morbidity and mortality from long-term microvascular and macrovascular complications. Evidence from randomized controlled trials indicates that aggressive treatment directed at improving glycemic control reduces the incidence of diabetes-related microvascular complications. Traditionally, oral monotherapy for type 2 diabetes is initiated when diet and exercise do not control hyperglycemia, followed by the sequential, stepwise addition of oral agents as glycemic control deteriorates. Insulin is the last therapeutic option used, generally reserved for advanced stages of the disease when multiple oral combination treatment fails. Despite a better understanding of the pathophysiologic disease mechanisms in the past decade, the expanded armamentarium of targeted oral antidiabetic drugs, and the conclusive evidence of the benefits of stringent glycemic control, actual treatment outcomes in clinical practice remain suboptimal relative to established treatment goals (glycosylated hemoglobin A1c level <7%). Earlier detection and aggressive treatment are critical to address the natural progression of diabetes because multiple defects (insulin resistance, insulin insufficiency, glucotoxicity, and lipotoxicity) and vascular complications may be present at the time of diagnosis. Acknowledging the inadequacy of traditional strategies and underscoring the importance of insulin as an integral part of the therapeutic armamentarium, clinical trends are moving toward earlier use of insulin combined with 1 or more oral agents. Such strategies can address the multiple abnormalities present early in the disease course and may restore optimal control. A new treatment paradigm for patients with type 2 diabetes to achieve and maintain near-normal glycemic control is warranted.