Clinical inquiries. What is the role of combination therapy (insulin plus oral medication) in type 2 diabetes?

Combination therapy using insulin plus metformin (Glucophage), a sulfonylurea, or both produces glycemic control comparable with using insulin alone, but there is less weight gain when metformin is used (strength of recommendation [SOR]: B, based on systematic review of randomized controlled trials [RCTs] with some heterogeneity). Combination therapy using insulin and pioglitazone (Actos) reduces glycosylated hemoglobin (Hb A1c) more than either insulin alone or adding pioglitazone to a sulfonylurea, but results in more weight gain (SOR: A, based on RCT). Using insulin glargine (Lantus) in combination therapy produces fewer nocturnal hypoglycemic events than using neutral protamine Hagedorn (NPH) insulin, while producing equivalent Hb A1c reduction (SOR: B, based on RCT). When the HbA1c is high (above 9.0% to 9.5%) on 1 or 2 oral agents, beginning combination therapy is more effective than adding another oral agent (SOR: B, based on subpopulation analysis in RCTs).