Perspective:

The following are key points about the management of hyperglycemia in type 2 diabetes mellitus:

1. The cornerstone of the pharmacological management of type 2 diabetes mellitus is a patient-centered approach that accounts for individual patient preferences and needs.

2. For most patients, efforts to lower glycosylated hemoglobin (HbA_1c) to <7.0% are justified to reduce the incidence of microvascular complications. Ideally, preprandial and postprandial glucose should be maintained at <130 mg/dl and <180 mg/dl, respectively.

3. Not all patients benefit from aggressive glucose management, and treatment target should be individualized. Less stringent goals for HbA_1c may be justified in some older patients and those with a history of severe hypoglycemia and/or major comorbidities. As healthier patients with relatively longer life expectancy accrue risk for vascular complications over time, lower glycemic targets (e.g., an HbA_1c <6.5-7.0%) may be warranted.

4. Personalized dietary changes and exercise remain the foundation of type 2 diabetes management. At diagnosis, highly motivated patients with an HbA_1c not exceeding about 7.5% could be given a trial of lifestyle modifications for a period of 3-6 months before embarking on pharmacotherapy.

5. Provided that it is not contraindicated, metformin remains first-line pharmacotherapy. Although previously contraindicated in heart failure, it can be used as long as ventricular dysfunction is not severe.

6. Current US guidelines caution against the use of metformin in patients with moderate degrees of renal insufficiency (>1.5 mg/dl in men and >1.4 mg/dl in women).

7. The use of two noninsulin oral agents or the use of insulin itself may be justified in patients with particularly high baseline HbA_1c (e.g., >9.0%) levels in whom monotherapy would be unlikely to be successful.

8. If an individualized, predetermined HbA_1c target is not achieved within 3 months of mono-pharmacotherapy, two-drug therapy or the introduction of basal insulin should be considered.

9. Pioglitazone, a thiazolidinedione, may reduce adverse cardiovascular events in patients with established macrovascular disease and is, therefore, an option in those patients with coronary artery disease. It should be avoided when heart failure is present.

10. Injectable GLP-1 receptor agonists (e.g., exenatide or liraglutide) that target the incretin system may be advantageous, owing to their association with at least modest weight loss and early reports of favorable changes to cardiovascular risk.