Perspective:

The following are 10 points to remember about this clinical practice guideline from the American College of Physicians (ACP).

1. Type 2 diabetes mellitus (DM) affects over 90% of patients with diabetes and approximately 25.8 million adults in the United States. Currently, 11 classes of drugs are approved by the Food and Drug Administration (FDA) for the treatment of hyperglycemia in the setting of DM. Among patients with DM, approximately 145 take both insulin and an oral medication, and 58% take an oral medication for control of hyperglycemia. The following are recommendations from the ACP’s practice guidelines regarding treatment of type 2 DM with oral therapies.

2. Based on a review of all clinical trials and cohorts, ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 DM when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence).

3. A review of prior studies suggests that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence).

4. Metformin appears more effective than other medications as monotherapy as well as when used in combination therapy with another agent for reducing glycemic hemoglobin levels, body weight, and plasma lipid levels in the majority of cases.

5. Regarding total mortality and cardiovascular mortality, the ACP believes it is currently difficult to draw conclusions about the comparative effectiveness of type 2 DM medications due to low-quality or insufficient evidence.

6. Regarding risk for hypoglycemia, the risk is increased with sulfonylureas compared to the risk associated with metformin or thiazolidinediones. The combination of metformin plus sulfonylureas is associated with 6 times more risk for hypoglycemia than the combination of metformin plus thiazolidinediones.

7. Metformin is associated with an increased risk for gastrointestinal side effects. Thiazolidinediones are associated with an increased risk for heart failure, and both rosiglitazone and pioglitazone are contraindicated in patients with serious heart failure.

8. Metformin is contraindicated in patients with impaired kidney function, decreased tissue perfusion or hemodynamic instability, liver disease, alcohol abuse, heart failure, and any condition that might lead to lactic acidosis.

9. Regarding specific subpopulations, the ACP believes the current evidence is not sufficient to show any difference in effectiveness among various medications across subgroups of adults.

10. The ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence).