NEW YORK (Reuters Health) – If lifestyle changes are not enough to control type 2 diabetes, metformin should be the first oral agent added to treatment, according to a new clinical practice guideline issued by the American College of Physicians and published in the Annals of Internal Medicine for February 7.

The recommendation is based on a review of studies comparing the effectiveness of different classes of oral diabetes drugs approved by the U.S. Food and Drug Administration: metformin, sulfonylureas, meglitinides, thiazolidinediones, inhibitors of dipeptidyl peptidase-4, and glucagon-like peptide-1 agonists.

“We found that most diabetes medications reduced blood sugar levels to a similar degree,” said Dr. Amir Qaseem, Director of Clinical Policy at ACP, in a press statement. “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 includes three recommendations. The first is to add oral pharmacologic therapy if diet, exercise and weight loss do not adequately improve hyperglycemia.

The panel drew on 104 head-to-head RCTs to compare the effects of various type 2 diabetes medications on HbA1c concentrations. Most agents had similar efficacy and reduced HbA1c by about 1 percentage point, although DPP-4 inhibitors were significantly less effective than metformin, according to the report.

Based on these findings, and the balance of side effects and safety factors, the second recommendation is to start oral treatment with metformin monotherapy.

If that fails to control glucose levels sufficiently, the third recommendation is to add another oral agent to metformin. “All dual-regimen combination therapies were more efficacious than monotherapy and reduced HbA1c levels by an average of 1 additional percentage point compared with monotherapy,” the authors found. However, there was insufficient evidence to recommend a specific combination of agents.

They also point out that adverse effects are more likely with combination treatment than with monotherapy. In particular, the combination of metformin plus a sulfonylurea is associated with a six-fold greater risk of hypoglycemia than the combination of metformin plus a thiazolidinedione.

Dr. Qaseem and colleagues note that they did not review combinations of more than two agents, and they add, “Although this guideline addresses only oral pharmacological therapy, patients with persistent hyperglycemia despite oral agents and lifestyle interventions may need insulin therapy.”

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