Pharmacokinetics and clinical evaluation of the alogliptin plus pioglitazone combination for type 2 diabetes

Abstract

Introduction: Type 2 diabetes is a complex disease with multiple defects, which generally requires a combination of several pharmacological approaches to reach glucose control targets. A unique fixed-dose combination combines a thiazolidinedione (pioglitazone) and a dipeptidyl peptidase-4 inhibitor (alogliptin).

Area covered: An extensive literature search was performed to analyze the pharmacokinetics of pioglitazone and alogliptin when used separately and in combination as well as to summarize clinical and toxicological considerations about the combined therapy.

Expert opinion: Pioglitazone, a potent insulin sensitizer, and alogliptin, an incretin-based agent that potentiates post-meal insulin secretion and reduces glucagon secretion, have complementary mechanisms of action. The clinical efficacy of a combined therapy is superior to any single therapy in patients treated with diet or with metformin (with or without sulphonylurea). These two drugs can be administered once daily, with or without a meal. No clinically relevant pharmacokinetic interactions between the two agents have been described and the fixed-dose combination has shown bioequivalence with alogliptin and pioglitazone given separately. Combining alogliptin with pioglitazone does not alter the safety profile of each compound. Weight gain observed with pioglitazone may be limited with the addition of alogliptin. The concern of an increased risk of heart failure remains to be better investigated.

Keywords:

• alogliptin
• combined therapy
• fixed-dose combination
• pharmacokinetics
• pioglitazone
• type 2 diabetes mellitus

Declaration of interest

AJ Scheen has received lecture/advisor fees from AstraZeneca/Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, NovoNordisk, Sanofi and Takeda. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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