title: Efficacy and safety of sitagliptin and the fixed-dose combination of sitagliptin and metformin vs. pioglitazone in drug-naïve patients with type 2 diabetes.
abstract: OBJECTIVE
  The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and moderate-to-severe hyperglycaemia (A1C = 7.5-12.0%).
  
  
  METHODS
  In an initial 12-week phase (Phase A), 492 patients were randomised 1 : 1 in a double-blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up-titrated to 30 mg after 6 weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET (up-titrated to 50/1000 mg bid over 4 weeks) and the PIO group was up-titrated to 45 mg qd
  
  
  RESULTS
  At the end of Phase A, mean changes from baseline were -1.0% and -0.9% for A1C; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose; and -52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO, respectively. At the end of Phase B, improvements in glycaemic parameters were greater with SITA/MET vs. PIO: -1.7% vs. -1.4% for A1C (p = 0.002); -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma glucose (p = 0.03); -90.3 mg/dl vs. -69.1 mg/dl for 2-h postmeal glucose (p = 0.001); and 55.0% vs. 40.5% for patients with A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of oedema were observed with SITA/MET vs. PIO. The incidence of hypoglycaemia was similarly low in both groups. Body weight decreased with SITA/MET and increased with PIO (-1.1 kg vs. 3.4 kg; p < 0.001).
  
  
  CONCLUSIONS
  Improvements in glycaemic control were greater with SITA/MET vs. PIO, with weight loss vs. weight gain. Both treatments were generally well tolerated.
authors.affiliation: Servicio de Endocrinología y Diabetes, Centro Médico Docente la Trinidad, Caracas, Venezuela.
authors.forename: A
authors.initials: A
authors.lastname: Pérez-Monteverde
authors.forename: T
authors.initials: T
authors.lastname: Seck
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: M A
authors.initials: MA
authors.lastname: Lee
authors.forename: C M
authors.initials: CM
authors.lastname: Sisk
authors.forename: D E
authors.initials: DE
authors.lastname: Williams-Herman
authors.forename: S S
authors.initials: SS
authors.lastname: Engel
authors.forename: K D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: B J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D008687:Metformin; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone