title: Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes.
abstract: BACKGROUND
  New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes (T2D), a progressive disorder that often requires combination therapy. The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D.
  
  
  METHODS
  The present study was a randomized double-blind placebo-controlled parallel-group 54-week study conducted at 41 sites across North and South America, Europe, and Asia in 278 patients with HbA1c ranging from ≥7.5% to ≤11.0% despite ongoing combination therapy with metformin (≥1500 mg/day) and rosiglitazone (≥4 mg/day). Patients were randomized (2:1) to receive sitagliptin 100 mg or placebo once daily. The main outcome measure was change from baseline in HbA1c at Week 18.
  
  
  RESULTS
  Mean baseline HbA1c was 8.8%. The mean placebo-adjusted change from baseline in HbA1c with sitagliptin treatment was -0.7% (P < 0.001) at Week 18 and -0.8% (P < 0.001) at Week 54. There were also significant (P < 0.001) reductions in 2-h post-meal glucose and fasting plasma glucose compared with placebo at Weeks 18 and 54. Significantly higher proportions of sitagliptin- than placebo-treated patients had HbA1c<7.0% at Weeks 18 (22% vs 9%; P = 0.003) and 54 (26% vs 14%; P = 0.015). Changes in body weight and the rates of adverse events overall, hypoglycemia, and gastrointestinal adverse events were similar in the sitagliptin and placebo groups during the 54-week study.
  
  
  CONCLUSIONS
  In patients with T2D, the addition of sitagliptin for 54 weeks to ongoing therapy with metformin and rosiglitazone improved glycemic control and was generally well tolerated compared with placebo.
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Adrian S
authors: AS
authors: Dobs
authors: Barry J
authors: BJ
authors: Goldstein
authors: Pablo
authors: P
authors: Aschner
authors: Edward S
authors: ES
authors: Horton
authors: Guillermo E
authors: GE
authors: Umpierrez
authors: Lorraine
authors: L
authors: Duran
authors: Julie S
authors: JS
authors: Hill
authors: Yu
authors: Y
authors: Chen
authors: Gregory T
authors: GT
authors: Golm
authors: Ronald B
authors: RB
authors: Langdon
authors: Debora E
authors: DE
authors: Williams-Herman
authors: Keith D
authors: KD
authors: Kaufman
authors: John M
authors: JM
authors: Amatruda
authors: Juan Camilo Arjona
authors: JC
authors: Ferreira
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010919:Placebos; D011719:Pyrazines; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; C517652:hemoglobin A1c protein, human