title: Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone--a factorial study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes.
  
  
  METHODS
  Patients with A1c ≥7.5 and ≤11.0% were randomized among seven arms that received, once daily, 100 mg sitagliptin alone; 15, 30 or 45 mg pioglitazone alone, or 100 mg sitagliptin plus 15, 30 or 45 mg pioglitazone for 54 weeks. The primary endpoint was change from baseline in A1c at week 24. Protocol-specified analyses compared combination therapies with monotherapies at respective dose-strengths and combination of sitagliptin plus pioglitazone 30 mg with pioglitazone 45 mg monotherapy. Post-hoc analyses compared sitagliptin plus pioglitazone 15 mg with pioglitazone monotherapy at the two higher doses.
  
  
  RESULTS
  Initial combination therapy with sitagliptin and pioglitazone provided significantly greater reductions in A1c (0.4-0.7% differences) and other glycaemic endpoints than either monotherapy at the same doses. Combining sitagliptin with low-dose pioglitazone generally produced greater glycaemic improvements than higher doses of pioglitazone monotherapy (0.3-0.4% differences in A1c). Combination therapy was generally well tolerated; adverse events (AEs) of hypoglycaemia were reported with similar incidence (7.8-11.1%) in all treatment groups over the 54 weeks of study; oedema was reported in 0.5% of patients in the sitagliptin monotherapy group and 2.7-5.3% among pioglitazone-treated groups. Significant weight gain was observed in all combination-treated groups compared with the sitagliptin monotherapy group.
  
  
  CONCLUSIONS
  Initial combination therapy with sitagliptin and pioglitazone provided better glycaemic control than either monotherapy and was generally well tolerated.
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA, USA; University of California San Diego, San Diego, CA, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
authors.forename: B
authors.initials: B
authors.lastname: Staels
authors.forename: V A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: M Z
authors.initials: MZ
authors.lastname: Chou
authors.forename: R
authors.initials: R
authors.lastname: Teng
authors.forename: G T
authors.initials: GT
authors.lastname: Golm
authors.forename: R B
authors.initials: RB
authors.lastname: Langdon
authors.forename: K D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: H
authors.initials: H
authors.lastname: Steinberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; glycaemic control; incretins; sitagliptin