title: Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin.
abstract: OBJECTIVE
  To compare the tolerability and efficacy of vildagliptin to pioglitazone as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy over 1-year duration.
  
  
  METHODS
  This 52-week, multicentre, randomized, active-controlled study compared vildagliptin (50 mg b.i.d., n = 295) and pioglitazone (30 mg daily, n = 281) in patients with inadequate glycaemic control [haemoglobin A1c (HbA(1c)) 7.5-11%] receiving a stable dose of metformin (>or=1500 mg). The primary objective was to demonstrate non-inferiority of vildagliptin at 24 weeks in the change in HbA(1c) from baseline. The objective of the additional 28 weeks of the study was to assess long-term safety, while also assessing mean change from baseline to study end in HbA(1c), fasting plasma glucose and body weight.
  
  
  RESULTS
  When added to a stable dose of metformin (mean baseline dose approximately 2 g/day), the non-inferiority of HbA(1c) lowering of vildagliptin to pioglitazone over 24 weeks was established at the non-inferiority margin of 0.3% (between-group difference = 0.1%). During the remaining 28 weeks, comparable HbA(1c) decreases were recorded in both groups. Overall adverse event (AE) rates were similar in both groups, as was the occurrence of peripheral oedema. Hypoglycaemia occurred rarely in both groups. Serious AEs occurred more frequently with pioglitazone group. While mean body weight increased significantly in the pioglitazone group (+2.6 kg) from baseline, there was no significant weight gain with vildagliptin (+0.2 kg).
  
  
  CONCLUSIONS
  When added to metformin, vildagliptin demonstrates favourable safety and tolerability over 1 year. Vildagliptin provided additional HbA(1c) lowering to that achieved with metformin alone and comparable to that achieved with pioglitazone, with only pioglitazone causing weight gain.
authors.affiliation: Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Perugia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bolli
authors.forename: F
authors.initials: F
authors.lastname: Dotta
authors.forename: L
authors.initials: L
authors.lastname: Colin
authors.forename: B
authors.initials: B
authors.lastname: Minic
authors.forename: M
authors.initials: M
authors.lastname: Goodman
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D000077205:Pioglitazone; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077597:Vildagliptin; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D000077205:Pioglitazone; D011759:Pyrrolidines; D045162:Thiazolidinediones; D000077597:Vildagliptin