title: Efficacy and safety of initial combination therapy with alogliptin plus metformin versus either as monotherapy in drug-naïve patients with type 2 diabetes: a randomized, double-blind, 6-month study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin plus metformin (A + M) initial combination therapy versus either as monotherapy in drug-naïve T2DM patients.
  
  
  METHODS
  This international, randomized, double-blind, placebo-controlled, 26-week study involved T2DM patients with hyperglycaemia (HbA1c 7.5-10.0%) following diet/exercise therapy. Patients (N = 784) received placebo, alogliptin (A, 12.5 mg BID or 25 mg QD), metformin (M, 500 or 1000 mg BID) or A + M (12.5/500 or 12.5/1000 mg BID); placebo, A25 for secondary analyses only.
  
  
  METHODS
  week 26 changes from baseline in HbA1c (primary), fasting plasma glucose (FPG) and 2-h postprandial glucose (PPG); incidences of clinical response and hyperglycaemic rescue.
  
  
  RESULTS
  Week 26 mean HbA1c reductions from baseline (8.45%) were -1.22 and -1.55% with A + M 12.5/500 and 12.5/1000 versus -0.56, -0.65, and -1.11% with A12.5, M500 and M1000 (p<0.001, A + M vs. component monotherapies). FPG reductions were -1.76 and -2.55 mmol/L with 12.5/500 and 12.5/1000 versus -0.54, -0.64 and -1.78 mmol/L with A12.5, M500 and M1000 (p < 0.05, A + M vs. component monotherapies). Significantly more A + M-treated patients achieved HbA1c < 7% (47.1-59.5% vs. 20.2-34.3% with monotherapy), significantly fewer required hyperglycaemic rescue (2.6-12.3% vs. 10.8-22.9% with monotherapy). A + M caused only mild/moderate hypoglycaemia (1.9-5.3%) and weight loss (0.6-1.2 kg).
  
  
  CONCLUSIONS
  Alogliptin plus metformin initial combination therapy was well tolerated yet more efficacious in controlling glycaemia in drug-naïve T2DM patients than either as monotherapy.
authors.affiliation: Florida Hospital, Sanford Burnham Medical Research Institute, Orlando, FL, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Pratley
authors.forename: P
authors.initials: P
authors.lastname: Fleck
authors.forename: C
authors.initials: C
authors.lastname: Wilson
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010880:Piperidines; D014498:Uracil; C517652:hemoglobin A1c protein, human; C520853:alogliptin
keywords: DPP-4; T2DM; alogliptin; coadministration; combination therapy; dipeptidyl peptidase-4 inhibitor; metformin; monotherapy; type 2 diabetes mellitus