title: The effect of alogliptin and pioglitazone combination therapy on various aspects of β-cell function in patients with recent-onset type 2 diabetes.
abstract: OBJECTIVE
  Type 2 diabetes mellitus (T2DM) management requires continuous treatment intensification due to progressive decline in β-cell function in insulin resistant individuals. Initial combination therapy of a dipeptidyl peptidase (DPP)-4 inhibitor with a thiazolidinedione (TZD) may be rational. We assessed the effects of the DPP4 inhibitor alogliptin (ALO) combined with the TZD pioglitazone (PIO), vs ALO monotherapy or placebo (PBO), on β-cell function and glycemic control in T2DM.
  
  
  METHODS
  A 16-week, two-center, randomized, double-blind, PBO-controlled, parallel-arm intervention study in 71 patients with well-controlled T2DM (age 59.1±6.3 years; A1C 6.7±0.1%) treated with metformin, sulfonylurea, or glinide monotherapy was conducted. Patients were treated with combined ALO 25 mg and PIO 30 mg daily or ALO 25 mg daily monotherapy or PBO. Main outcome measures included change in A1C and fasting plasma glucose (FPG) from baseline to week 16. In addition, change in β-cell function parameters obtained from standardized meal tests at baseline and at week 16 was measured.
  
  
  RESULTS
  ALO/PIO and ALO decreased A1C from baseline by 0.9±0.1 and 0.4±0.2% respectively (both P<0.001 vs PBO). FPG was decreased to a greater extent by ALO/PIO compared with ALO monotherapy (P<0.01). ALO/PIO treatment improved β-cell glucose sensitivity (vs PBO; P<0.001) and fasting secretory tone (vs PBO; P=0.001), while ALO monotherapy did not change β-cell function parameters. All treatments were well tolerated.
  
  
  CONCLUSIONS
  Short-term treatment with ALO/PIO or ALO improved glycemic control in well-controlled T2DM patients, but only combined ALO/PIO improved β-cell function. These data support that initial combination therapy with a DPP4 inhibitor and TZD to address multiple core defects in T2DM may be a sensible approach.
authors.affiliation: Diabetes Center, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: Van Raalte
authors.forename: Renate E
authors.initials: RE
authors.lastname: van Genugten
authors.forename: Björn
authors.initials: B
authors.lastname: Eliasson
authors.forename: Diane L
authors.initials: DL
authors.lastname: Möller-Goede
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Craig
authors.initials: C
authors.lastname: Wilson
authors.forename: Penny
authors.initials: P
authors.lastname: Fleck
authors.forename: Marja R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000368:Aged; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010880:Piperidines / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D010880:Piperidines; D045162:Thiazolidinediones; D014498:Uracil; C517652:hemoglobin A1c protein, human; C520853:alogliptin