title: Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study.
abstract: OBJECTIVE
  The purpose of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor vildagliptin in combination with the thiazolidinedione (TZD) pioglitazone in patients with type 2 diabetes (T2DM).
  
  
  METHODS
  This was a 24-week, multicentre, double-blind, randomized, parallel-group study comparing the effects of vildagliptin (50 or 100 mg daily) with placebo as an add-on therapy to pioglitazone (45 mg daily) in 463 patients with T2DM inadequately controlled by prior TZD monotherapy. Between-treatment comparisons of efficacy parameters were made by analysis of covariance model.
  
  
  RESULTS
  The adjusted mean change (AM Delta) in haemoglobin A(1c) from baseline to endpoint was -0.8 +/- 0.1% (p = 0.001 vs. placebo) and -1.0 +/- 0.1% (p < 0.001 vs. placebo), respectively, in patients receiving vildagliptin 50 or 100 mg daily. Relative to baseline, vildagliptin added to pioglitazone also reduced fasting plasma glucose (FPG) (AM Delta FPG =-0.8 +/- 0.2 mmol/l and -1.1 +/- 0.2 mmol/l; not significant (NS) vs. placebo) and postprandial glucose (PPG) [AM Delta PPG =-1.9 +/- 0.6 mmol/l and -2.6 +/- 0.6 mmol/l (p = 0.008 vs. placebo)] for 50 and 100 mg daily respectively. Relative to placebo, both doses of vildagliptin significantly increased the insulin secretory rate/glucose by more than threefold. The overall incidence of adverse events (AEs) was 55.5, 50.0 and 48.7% in patients receiving vildagliptin 50 mg, 100 mg daily or placebo respectively. Serious AEs were experienced by 6.8, 1.3 and 5.7% of patients receiving vildagliptin 50 mg, 100 mg daily or placebo respectively. Mild hypoglycaemia was reported by 0, 0.6 and 1.9% of patients, respectively, receiving vildagliptin 50 mg, 100 mg daily or placebo.
  
  
  CONCLUSIONS
  Vildagliptin is effective and well tolerated when added to a maximum dose of pioglitazone, without increasing the risk of hypoglycaemia.
authors.affiliation: Division of Endocrinology, Baylor College of Medicine, Houston, TX 77030, USA. agarber@bcm.tmc.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Garber
authors.forename: A
authors.initials: A
authors.lastname: Schweizer
authors.forename: M A
authors.initials: MA
authors.lastname: Baron
authors.forename: E
authors.initials: E
authors.lastname: Rochotte
authors.forename: S
authors.initials: S
authors.lastname: Dejager
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology; D008024:Ligands; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D000077205:Pioglitazone; D011384:Proinsulin / Q000097:blood; D011480:Protease Inhibitors / Q000627:therapeutic use; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008024:Ligands; D008055:Lipids; D009570:Nitriles; D000077205:Pioglitazone; D011384:Proinsulin; D011480:Protease Inhibitors; D011759:Pyrrolidines; D045162:Thiazolidinediones; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human; C089946:2,4-thiazolidinedione; C042807:DPP4 protein, human