title: Efficacy and safety of a single-pill combination of vildagliptin and metformin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  The use of dipeptidyl peptidase-4 inhibitors in combination with metformin is increasing in Japanese patients with type 2 diabetes mellitus (T2DM), but no single-pill combination (SPC) is currently available in Japan. The objective of this study was to assess the efficacy and safety of vildagliptin/metformin SPC in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapy.
  
  
  METHODS
  This was a 14-week, randomized, double-blind, parallel-group, placebo-controlled trial. 171 patients with T2DM inadequately controlled [HbA1c (glycosylated hemoglobin) 7.0-10.0%] with vildagliptin 50 mg twice daily (bid) were randomized (2:1) to receive either a vildagliptin/metformin SPC (n = 115) or matching vildagliptin/placebo SPC (n = 56).
  
  
  RESULTS
  Baseline demographics and background characteristics were generally comparable between the treatment groups. The change in HbA1c [mean ± standard error (SE)] was -0.8 ± 0.1% in the vildagliptin/metformin SPC (baseline HbA1c, 7.9 ± 0.1%) group and 0.1 ± 0.1% in the vildagliptin/placebo SPC (baseline HbA1c, 8.0 ± 0.1%) group, with a between-treatment difference of -1.0 ± 0.1% (P <0.001) in favor of the vildagliptin/metformin SPC group. The proportion of patients achieving target HbA1c <7.0% was significantly higher with vildagliptin/metformin SPC compared with vildagliptin/placebo SPC (45.8% vs. 13.5%, P <0.001). The overall incidences of adverse events (AEs) were 43.5% in the vildagliptin/metformin SPC and 67.9% in the vildagliptin/placebo SPC group. The incidences of serious AEs were low in both the treatment groups (0.9% vs. 3.6%, respectively). Body weight remained constant throughout the study in both the treatment groups. There were no deaths or hypoglycemic events during the study.
  
  
  CONCLUSIONS
  Switching Japanese patients with T2DM requiring treatment intensification, from vildagliptin monotherapy to a vildagliptin/metformin SPC (50/250 or 50/500 mg) was efficacious and safe, eliciting significant reduction in HbA1c without increased risk of hypoglycemia and weight gain.
authors.affiliation: The Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University, Tokyo, Japan, odawara@tokyo-med.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
authors.forename: Mika
authors.initials: M
authors.lastname: Yoshiki
authors.forename: Misako
authors.initials: M
authors.lastname: Sano
authors.forename: Izumi
authors.initials: I
authors.lastname: Hamada
authors.forename: Valentina
authors.initials: V
authors.lastname: Lukashevich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kothny