title: Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study.
abstract: OBJECTIVE
  To assess the efficacy and safety of adding alogliptin versus uptitrating pioglitazone in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone.
  
  
  METHODS
  In this randomized, double-blind, active-controlled, parallel-group study, patients with type 2 diabetes and A1c ≥7.0 and ≤10.0% on metformin (≥1500 mg or maximum tolerated dose; Met) and pioglitazone 30 mg (Pio30) received alogliptin 25 mg (Alo25; n = 404) or pioglitazone 15 mg (n = 399) added to Met+Pio30 for 52 weeks. The primary endpoint was change from baseline (CFB) in A1c at weeks 26 and 52, with sequential testing for non-inferiority of Met+Pio30+Alo25 at weeks 26 and 52 and then for superiority at week 52.
  
  
  RESULTS
  Met+Pio30+Alo25 showed superior glycaemic control versus Met+Pio45 at week 52 [least squares (LS) mean CFB in A1c, -0.70 vs. -0.29%; p < 0.001]. At week 52, Met+Pio30+Alo25 resulted in greater CFB in A1c regardless of baseline A1c (p < 0.001); higher proportions of patients achieving A1c ≤7.0 (33.2 vs. 21.3%) and ≤6.5% (8.7 vs. 4.3%; p < 0.001); greater CFB in fasting plasma glucose (FPG; LS mean CFB, -0.8 vs. -0.2 mmol/L; p < 0.001); and greater improvements in measures of β-cell function (p < 0.001). Hypoglycaemia incidence was low (Met+Pio30+Alo25, 4.5%; Met+Pio45, 1.5%), mostly mild to moderate, but with two severe events in the Met+Pio30+Alo25 group. No meaningful differences in incidences of individual adverse events were observed between treatments.
  
  
  CONCLUSIONS
  Adding alogliptin to an existing metformin-pioglitazone regimen provided superior glycaemic control and potentially improved β-cell function versus uptitrating pioglitazone in patients with type 2 diabetes, with no clinically important differences in safety.
authors: Department of Internal Medicine, Diabetes & Endocrinology Unit, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy. bosi.emanuele@hsr.it
authors: E
authors: E
authors: Bosi
authors: G C
authors: GC
authors: Ellis
authors: C A
authors: CA
authors: Wilson
authors: P R
authors: PR
authors: Fleck
mesh_terms: D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D010880:Piperidines; D045162:Thiazolidinediones; D014498:Uracil; C517652:hemoglobin A1c protein, human; C520853:alogliptin