Tight control of hyperglycemia in type 2 diabetes mellitus

Background: In the past decade, a number of new therapeutic agents have been introduced for the treatment of patients with type 2 diabetes mellitus (DM). These agents target the metabolic disturbances that characterize this disease, specifically insulin resistance, excessive hepatic gluconeogenesis, and β-cell failure. Objective: The goal of this article was to review the options available for obtaining glycemic control in patients with type 2 DM. Methods: Materials for this article were identified through searches (1965-present) of MEDLINE (English language only). Search terms included treatment of type 2 diabetes, insulin therapy, oral hypoglycemic therapy, and exenatide. Results: Large randomized controlled trials have shown that the incidence of microvascular complications of DM can be greatly reduced by improving glycemic control. The cornerstone of glycemic control continues to be successful implementation of a diet and exercise program. These dietary modifications reduce obesity, lower glucose levels, and improve insulin sensitivity. Lifestyle changes, however, are difficult to achieve and sustain in unsupervised settings. For patients who do not respond adequately to diet and exercise therapy alone after a 3-month trial, the addition of pharmacotherapy to the treatment regimen is indicated. Five classes of oral agents are now approved by the US Food and Drug Administration for the treatment of type 2 DM: the sulfonylureas and meglitinides (both secretagogues), the biguanides (metformin), the a-glucosidase inhibitors (acarbose and miglitol), and the thiazolidinediones (rosiglitazone and pioglitazone). The recently approved glucagon-like peptide-1 analogue exenatide is an injectable hypoglycemic agent that may also be considered before starting patients on insulin. Long-term clinical trials have found that over time, most patients will require combination therapy to achieve adequate glycemic control. Insulin therapy is indicated when glycemic control cannot be achieved and maintained with lifestyle intervention, including diet and exercise, and pharmacologic treatment with oral antidiabetic agents or exenatide. Conclusions: By combining lifestyle interventions with selected pharmacologic agents, clinicians are now able to individualize treatment regimens to better control hyperglycemia, and to help prevent the development of diabetic microvascular and macrovascular complications.