Advantages and Pitfalls of Antihyperglycemic Combination Pills as First-Line Therapy in the Management of Type 2 Diabetes.

Type 2 diabetes is a heterogeneous disease with multiple underlying pathophysiological processes. Several new antidiabetic agents are presently available for clinical use, yet very few clinical trials have been performed on the efficacy of combination pill therapy. Combination pill use is easily justified as a second-line therapy in which the advantages of added efficacy, enhanced adherence, and only modest increase in risk are recognized. In contrast, combination pill use as first-line therapy has some drawbacks, such as increased risk of hypoglycemia, difficulty in attribution of side effects to the constituents, and less than additive efficacy of the components of the pill. In general, combinations of drugs with synergistic mechanisms of action are preferable. However, the efficacy of currently available combination pills when used as first-line therapy is less than the sum of the efficacy of its components. The current guidelines recommend initiation of dual therapy in drug-naive individuals depending on baseline HbA1c at the time of diagnosis. When the HbA1c is above 8.5%-9%, the likelihood of achieving glycemic targets with a single agent diminishes sharply. These patients may be better candidates for treatment with a combination of antihyperglycemic agents as first-line therapy.