The Effect of Alogliptin and Metformin Combination Therapy in Type 2 Diabetes: A Pilot Study

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Background: As type 2 diabetes is characterized by both insulin resistance and impaired insulin secretion, oral anti-diabetic treatments including dipeptidyl peptidase-4 inhibitors, which stimulate insulin secretion, and biguanides, which enhance insulin sensitivity should be considered. Therefore, we performed a pilot study using a combination therapy with agents from both of these classes of drugs. We selected alogliptin and metformin as representative drugs and evaluated their combinational efficacy in patients with type 2 diabetes. Methods: Continuous glucose monitoring (CGM) was performed throughout the study for two patients with type 2 diabetes and one control subject. First, the subjects received no medication (the 5-day washout period), and later, all subjects received three patterns of medication: alogliptin alone, alogliptin and metformin co-administration, and metformin alone. Blood was sampled before and 1 h after breakfast and lunch on representative days during each treatment condition. Results: The CGM results indicated that combination of alogliptin and metformin attenuated the escalation and fluctuation of glucose levels. The patterns of insulin and glucagon secretion with alogliptin alone, alogliptin and metformin co-administration, and metformin alone varied among subjects. When alogliptin and metformin were co-administered, glucagon-like peptide-1 (GLP-1) levels 1 h after lunch were higher in all subjects compared to those at any other time point. Postprandial glucose-dependent insulinotropic peptide (GIP) levels varied according to medication and the subject. Conclusions: Thus, CGM results revealed that a combination of alogliptin and metformin effectively reduced postprandial glucose fluctuation and stabilized blood glucose levels. The study subjects exhibited completely different response patterns of insulin, glucagon, GLP-1, and GIP with medications alone or in combination, suggesting that individual hormone-dependent glycemic responses to these drugs are complicated and multifactorial. J Endocrinol Metab. 2013;3(4-5):111-118 doi: https://doi.org/10.4021/jem196e