title: Profile of saxagliptin in the treatment of type 2 diabetes: focus on Japanese patients.
abstract: Saxagliptin is a selective and potent dipeptidyl peptidase (DPP)-4 inhibitor, approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM) in the USA on July 2009, and had been launched globally in over 86 countries by September 2013. In patients with T2DM, once-daily administration of saxagliptin before breakfast achieves sustained inhibition of plasma DPP-4 activity and reduction of postprandial hyperglycemia, including after dinner, associated with an increase in plasma glucagon-like peptide-1 levels. This paper reviews the safety and efficacy of saxagliptin in Japanese patients with T2DM. The clinical development study in Japan supported its usefulness for the disease. Saxagliptin 1, 2.5, and 5 mg led to significant improvements in glycated hemoglobin (HbA1c), and was generally well tolerated. Treatment with saxagliptin 5 mg induced a sustained reduction in HbA1c over 52 weeks. Long-term combination therapy with saxagliptin and other oral hypoglycemic agents also provided sustained glycemic control and was well tolerated for up to 52 weeks. Saxagliptin as add-on to sulfonylureas or glinides has a tendency to increase hypoglycemia, but not with other oral antidiabetic agents, such as α-glucosidase inhibitors, metformin, or thiazolidinediones. The results of clinical trials have confirmed the long-term efficacy and safety of saxagliptin monotherapy as well as its use as add-on combination therapy, and support its usefulness as a therapeutic agent for T2DM. Saxagliptin has less concern for hypoglycemia and weight gain, which often becomes problematic in routine care of T2DM. Meta-analysis of clinical trials in the USA showed no evidence of increased risk of cardiovascular events associated with saxagliptin, suggesting the superior of saxagliptin in terms of safety. Recently, investigators in the SAVOR-TIMI (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction) 53 study suggested that DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, although the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. Saxagliptin is applicable for various pathological conditions, and is considered to be clinically significant as a new therapeutic option for Japanese patients with T2DM.
authors: Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Japan.
authors: Hiroyuki
authors: H
authors: Konya
authors: Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Japan.
authors: Yuzo
authors: Y
authors: Yano
authors: Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Japan.
authors: Satoshi
authors: S
authors: Matsutani
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Taku
authors: T
authors: Tsunoda
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Takashi
authors: T
authors: Ikawa
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Yoshiki
authors: Y
authors: Kusunoki
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Toshihiro
authors: T
authors: Matsuo
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Masayuki
authors: M
authors: Miuchi
authors: Division of Innovative Diabetes Treatment, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Tomoyuki
authors: T
authors: Katsuno
authors: Division of Diabetes, Department of Internal Medicine, Itami City Hospital, Itami, Hyogo, Japan.
authors: Tomoya
authors: T
authors: Hamaguchi
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Jun-Ichiro
authors: J
authors: Miyagawa
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Mitsuyoshi
authors: M
authors: Namba
keywords: Japan; dipeptidyl peptidase-4; efficacy; incretin hormones; patient acceptability; safety; saxagliptin; type 2 diabetes mellitus