The Food and Drug Administration issued a "black box" alert for rosiglitazone (Avandia) in 2007, warning that it increased the risk of heart attack. That followed an earlier warning that the medication, along with the related drug pioglitazone (Actos), increases heart-failure risk. Other evidence, in contrast, shows that an older and cheaper drug called metformin (Glucophage and generic) not only works as well as other drugs, but also lowers LDL cholesterol and triglycerides, doesn't seem to cause weight gain, and is less likely to cause a dangerous drop in blood sugar levels.

Our take

The newest drug classes—including the glitazones, meglitinides and nateglinides (Prandin, Starlix), alphaglucosidase inhibitors (Glyset, Precose), sitagliptin (Januvia), and the injectable exenatide (Byetta)—are no more effective or safer than metformin and another class of drugs known as sulfonylureas. Most people should usually start with metformin, using one of the others as a backup or additional drug if necessary. Those who don't normalize their blood sugar with pills should talk with their doctor about adding an injection of long-acting insulin to their regimen.