title: A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus.
abstract: OBJECTIVE
  To develop a longitudinal statistical model to indirectly estimate the comparative efficacies of two drugs, using model-based meta-analysis (MBMA). Comparison of two oral dipeptidyl peptidase (DPP)-4 inhibitors, sitagliptin and linagliptin, for type 2 diabetes mellitus (T2DM) treatment was used as an example.
  
  
  METHODS
  Systematic review with MBMA.
  
  
  METHODS
  MEDLINE, EMBASE, http://www.ClinicalTrials.gov, Cochrane review of DPP-4 inhibitors for T2DM, sitagliptin trials on Food and Drug Administration website to December 2011 and linagliptin data from the manufacturer.
  
  
  METHODS
  Double-blind, randomised controlled clinical trials, ≥12 weeks' duration, that analysed sitagliptin or linagliptin efficacies as changes in glycated haemoglobin (HbA1c) levels, in adults with T2DM and HbA1c >7%, irrespective of background medication. MODEL DEVELOPMENT AND APPLICATION: A Bayesian model was fitted (Markov Chain Monte Carlo method). The final model described HbA1c levels as function of time, dose, baseline HbA1c, washout status/duration and ethnicity. Other covariates showed no major impact on model parameters and were not included. For the indirect comparison, a population of 1000 patients was simulated from the model with a racial composition reflecting the average racial distribution of the linagliptin trials, and baseline HbA1c of 8%.
  
  
  RESULTS
  The model was developed using longitudinal data from 11 234 patients (10 linagliptin, 15 sitagliptin trials), and assessed by internal evaluation techniques, demonstrating that the model adequately described the observations. Simulations showed both linagliptin 5 mg and sitagliptin 100 mg reduced HbA1c by 0.81% (placebo-adjusted) at week 24. Credible intervals for participants without washout were -0.88 to -0.75 (linagliptin) and -0.89 to -0.73 (sitagliptin), and for those with washout, -0.91 to -0.76 (linagliptin) and -0.91 to -0.75 (sitagliptin).
  
  
  CONCLUSIONS
  This study demonstrates the use of longitudinal MBMA in the field of diabetes treatment. Based on an example evaluating HbA1c reduction with linagliptin versus sitagliptin, the model used seems a valid approach for indirect drug comparisons.
authors.affiliation: Endocrine Division, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sol, Brazil.
authors.forename: Jorge Luiz
authors.initials: JL
authors.lastname: Gross
authors.forename: James
authors.initials: J
authors.lastname: Rogers
authors.forename: Daniel
authors.initials: D
authors.lastname: Polhamus
authors.forename: William
authors.initials: W
authors.lastname: Gillespie
authors.forename: Christian
authors.initials: C
authors.lastname: Friedrich
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Brigitta Ursula
authors.initials: BU
authors.lastname: Monz
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.forename: Alexander
authors.initials: A
authors.lastname: Staab
authors.forename: Silke
authors.initials: S
authors.lastname: Retlich