New ACP Guidelines for Type 2 Diabetes Treatment

The new recommendations from the American College of Physicians (ACP) are based on a systematic evidence review and comparative efficacy analysis of FDA-approved oral medications for the treatment of type 2 diabetes (metformin, sulfonylureas, meglitinides, thiazolidinediones, DPP-4 inhibitors, and GLP-1 receptor antagonists).

Lead author Amir Qaseem, MD, FACP, PhD, MHA, director of clinical policy at the ACP said, "We found that most diabetes medications reduced blood sugar levels to a similar degree." "However, metformin is more effective compared to other type 2 diabetes drugs in reducing blood sugar levels when used alone and in combination with other drugs. In addition, metformin reduces body weight and improves cholesterol profiles."

The guideline authors searched MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials for trials that compared diabetes drugs head-to-head and were published in English-language journals between 1966 and April 2010. The researchers assessed clinical outcomes including death from any cause, cardiovascular disease and death, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. The ACP clinical practice guidelines grading system allowed grading of the recommendations and underlying evidence.

Specific recommendations in the new guidelines are:

• Recommendation 1: When diet, exercise, weight loss, and other lifestyle modifications have not adequately improved hyperglycemia, clinicians should add oral pharmacologic therapy in patients with type 2 diabetes (grade: strong recommendation, high-quality evidence).
• Recommendation 2: For most patients with type 2 diabetes, initial pharmacologic therapy should be monotherapy with metformin (grade: strong recommendation; high-quality evidence).
• Recommendation 3: When lifestyle modifications and monotherapy with metformin fail to control hyperglycemia, clinicians should add a second drug to metformin (grade: strong recommendation; high-quality evidence).

Overall adverse effects were fewer with metformin than with sulfonylureas, and high-quality evidence showed that risk for dangerous levels of hypoglycemia was higher with sulfonylureas than with metformin or thiazolidinediones. In addition, the combination of metformin plus sulfonylureas is associated with 6-fold greater risk for hypoglycemia than the combination of metformin plus thiazolidinediones. When used as monotherapy, the risk for hypoglycemia with metformin and thiazolidinediones was similar, based on moderate-quality evidence.

Evidence was insufficient regarding any efficacy difference among various medications across subgroups of adults based on age, sex, or race.

The ACP recommended generic metformin because of its better efficacy and fewer adverse effects than most other available medications, lack of associated weight gain, and lower cost.

The guideline authors wrote, "It was difficult to draw conclusions about the comparative effectiveness of type 2 diabetes medications on all-cause and cardiovascular mortality, cardiovascular and cerebrovascular morbidity, and microvascular outcomes because of low-quality or insufficient evidence." "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."

• Note that in a new guideline, the American College of Physicians (ACP) recommends monotherapy with metformin as the initial pharmacologic therapy for most patients with type 2 diabetes.
• Note that the ACP recommends the addition of a second agent when patients have persistent hyperglycemia despite metformin and lifestyle modification.

Ann Intern Med. 2012;156:218-231.