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


METHODS
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.


CONCLUSIONS
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.
University of Liège, Center for Interdisciplinary Research on Medicines (CIRM), Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU Sart Tilman , Liège , Belgium +32 4 3667238 ; +32 4 3667068 ; andre.scheen@ chu.ulg.ac.be.
André J
AJ
Scheen
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000077205:Pioglitazone; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D045162:Thiazolidinediones; D014498:Uracil; C520853:alogliptin; D000077205:Pioglitazone
alogliptin; combined therapy; fixed-dose combination; pharmacokinetics; pioglitazone; type 2 diabetes mellitus