Pleiotropic effects of sitagliptin versus voglibose in patients with type 2 diabetes inadequately controlled via diet and/or a single oral antihyperglycemic agent: a multicenter, randomized trial.
OBJECTIVE
A step-up strategy for diet therapy and/or single oral antihyperglycemic agent (OHA) regimens has not yet been established. The aim of this study was to evaluate hemoglobin A1c (HbA1c) as a primary end point, and the pleiotropic effects on metabolic and cardiovascular parameters as secondary end points, of sitagliptin versus voglibose in patients with type 2 diabetes with inadequate glycemic control while on diet therapy and/or treatment with a single OHA.


METHODS
In this multicenter, randomized, open-label, parallel-group trial, a total of 260 patients with inadequately controlled type 2 diabetes (HbA1c levels >6.9%) were randomly assigned to receive either sitagliptin (50 mg, once daily) or voglibose (0.6 mg, thrice daily) for 12 weeks. The primary end point was HbA1c levels.


RESULTS
Patients receiving sitagliptin showed a significantly greater decrease in HbA1c levels (-0.78±0.69%) compared with those receiving voglibose (-0.30±0.78%). Sitagliptin treatment also lowered serum alkaline phosphatase levels and increased serum creatinine, uric acid, cystatin-C and homeostasis model assessment-β values. Voglibose increased low-density lipoprotein-cholesterol levels and altered serum levels of several fatty acids, and increased Δ-5 desaturase activity. Both drugs increased serum adiponectin. The incidence of adverse events (AEs) was significantly lower in the sitagliptin group, due to the decreased incidence of gastrointestinal AEs.


CONCLUSIONS
Sitagliptin shows superior antihyperglycemic effects compared with voglibose as a first-line or second-line therapy. However, both agents possess unique pleiotropic effects that lead to reduced cardiovascular risk in Japanese people with type 2 diabetes.


BACKGROUND
UMIN 000003503.
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Yukiko
Y
Matsushima
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Yumie
Y
Takeshita
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Yuki
Y
Kita
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Toshiki
T
Otoda
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Ken-Ichiro
K
Kato
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Hitomi
H
Toyama-Wakakuri
ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa , Japan.
Hiroshi
H
Akahori
ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa , Japan.
Akiko
A
Shimizu
ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa , Japan.
Erika
E
Hamaguchi
ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa , Japan.
Yasuyuki
Y
Nishimura
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Takehiro
T
Kanamori
Department of Disease Control and Homeostasis , Kanazawa University Graduate School of Medical Sciences , Kanazawa, Ishikawa , Japan.
Shuichi
S
Kaneko
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan; ERA-DM Chapter 1 Study Group, Kanazawa, Ishikawa, Japan.
Toshinari
T
Takamura
A1C; Drug Therapy; Fatty Acid Desaturase(s)