Alogliptin-Pioglitazone Combination Therapy: A Rational Approach to Treating Type 2 Diabetes Mellitus

Introduction: Type 2 diabetes mellitus (T2DM) is a complex disease with a number of metabolic abnormalities. At present, treatment typically proceeds in a stepwise fashion, beginning with diet and exercise followed by incremental additions of oral antidiabetic agents as required to achieve and maintain glycemic control (glycosylated hemoglobin [HbA 1c ] ≤6.9% and 6.5%, respectively). This approach is reactive rather than proactive as progression to the next level is based on treatment failure (i.e., not achieving target HbA 1c levels). Newer approaches to treatment of T2DM advocate early use of combination antihyperglycemic regimens with complementary mechanisms of action to correct multiple pathophysiologic defects, but this can impact negatively on treatment adherence. Fixed-dose combinations are associated with higher compliance rates than therapy with individual components administered concomitantly. This review examines evidence for a fixed-dose combination of alogliptin and pioglitazone recently approved for use in Japanese patients with T2DM. Methods: A MEDLINE search identified five randomized, controlled trials in which alogliptin and pioglitazone were used in combination to treat T2DM, and these form the basis of the review. Results: One study evaluated alogliptin-pioglitazone combination therapy in drug-naïve patients. In the remaining studies, alogliptin was evaluated as add-on therapy in patients with inadequate glycemic control despite treatment with pioglitazone (± metformin or sulfonylurea). In all studies, alogliptin-pioglitazone combination therapy consistently produced statistically significant reductions in HbA 1c of approximately 0.6–1.0% over and above those produced by either agent alone. This improvement was paralleled by improvements in fasting plasma glucose, proportions of patients achieving target HbA 1c levels and several other measures of glycemic control, including markers of beta-cell function. The alogliptin-pioglitazone combination was well tolerated across all studies. Conclusion: Alogliptin-pioglitazone combination therapy represents a rational approach to treatment of T2DM as the complementary mechanisms target several aspects of impaired glucose control. The fixed-dose combination offers scope for enhanced patient compliance and improved treatment outcomes.