A new clinical practice guideline from the American College of Physicians (ACP) recommends that metformin should be the initial drug used to treat most patients with type 2 diabetes when lifestyle modifications fail to control hyperglycemia. If needed, a second drug can also be added in combination with metformin. The new recommendations, published online February 6 in the Annals of Internal Medicine, are based on a systematic evidence review evaluating pertinent literature and comparative efficacy analysis of FDA approved oral medications for the treatment of type 2 diabetes. In a news release, Amir Qaseem, MD, FACP, PhD, MHA, director of clinical policy at the ACP, indicated that “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 (from 1966 through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials for studies that compared diabetes drugs and were published in English. 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 was used to grade the recommendations and underlying evidence. Specific recommendations in the new guidelines are: Recommendation 1: When lifestyle modifications including diet, exercise, and weight loss 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, clinicians should initially prescribe monotherapy with metformin (Grade: strong recommendation; high-quality evidence). Recommendation 3: When lifestyle modifications and monotherapy with metformin fail to control hyperglycemia, a second agent should be added to metformin (Grade: strong recommendation; high-quality evidence). Based on the evidence, metformin was more effective than other diabetes medications as monotherapy as well as when used in combination therapy. Metformin effectively lowered HbA1c levels, decreased body weight, and reduced plasma lipid levels in most cases. Regarding the comparative effectiveness of type 2 diabetes medications on all-cause and cardiovascular mortality, cardiovascular and cerebrovascular morbidity, and microvascular outcomes, the evidence was insufficient to make any recommendations. When compared with sulfonylureas, overall adverse effects were fewer with metformin and high-quality evidence showed that risk of hypoglycemia was higher with sulfonylureas than with metformin or thiazolidinediones. Additionally, the combination of metformin plus sulfonylureas was associated with a greater risk for hypoglycemia than the combination of metformin plus thiazolidinediones. Based on moderate-quality evidence, when used as monotherapy, the risk for hypoglycemia with metformin and thiazolidinediones was similar. Evidence was insufficient regarding the differential effectiveness among various medications as a function of age, sex, or race. References: Qaseem A, Humphrey L, Sweet D, et al. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. 2012;156:218-231.