Pioglitazone and rosiglitazone can be employed as oral therapy in patients with type 2 diabetes and preserved endogenous insulin secretion. Potential benefits and risks of each agent should be considered. An acceptable initial target for HbA1c is 7%. Lowering HbA1c to 6.5% did not reduce macrovascular complications in patients with type 2 diabetes, but did reduce new or worsening nephropathy. Aggressive therapy aiming to lower HbA1c to <6% in patients with type 2 diabetes at especially high risk of cardiovascular disease may lead to a higher risk of mortality.