title: Multivariate Prediction Equations for HbA1cLowering, Weight Change, and Hypoglycemic Events Associated with Insulin Rescue Medication in Type 2 Diabetes Mellitus: Informing Economic Modeling.
abstract: Type 2 diabetes mellitus (T2DM) is chronic and progressive and the cost-effectiveness of new treatment interventions must be established over long time horizons. Given the limited durability of drugs, assumptions regarding downstream rescue medication can drive results. Especially for insulin, for which treatment effects and adverse events are known to depend on patient characteristics, this can be problematic for health economic evaluation involving modeling.
  
  
  
  To estimate parsimonious multivariate equations of treatment effects and hypoglycemic event risks for use in parameterizing insulin rescue therapy in model-based cost-effectiveness analysis.
  
  
  
  Clinical evidence for insulin use in T2DM was identified in PubMed and from published reviews and meta-analyses. Study and patient characteristics and treatment effects and adverse event rates were extracted and the data used to estimate parsimonious treatment effect and hypoglycemic event risk equations using multivariate regression analysis.
  
  
  
  Data from 91 studies featuring 171 usable study arms were identified, mostly for premix and basal insulin types. Multivariate prediction equations for glycated hemoglobin A1clowering and weight change were estimated separately for insulin-naive and insulin-experienced patients. Goodness of fit (R2) for both outcomes were generally good, ranging from 0.44 to 0.84. Multivariate prediction equations for symptomatic, nocturnal, and severe hypoglycemic events were also estimated, though considerable heterogeneity in definitions limits their usefulness.
  
  
  
  Parsimonious and robust multivariate prediction equations were estimated for glycated hemoglobin A1cand weight change, separately for insulin-naive and insulin-experienced patients. Using these in economic simulation modeling in T2DM can improve realism and flexibility in modeling insulin rescue medication.
authors.affiliation: The Swedish Institute for Health Economics, Lund, Sweden. Electronic address: michael.willis@ihe.se.
authors.forename: Michael
authors.initials: M
authors.lastname: Willis
authors.affiliation: The Swedish Institute for Health Economics, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Asseburg
authors.affiliation: The Swedish Institute for Health Economics, Lund, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Nilsson
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Johnsson
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Bernt
authors.initials: B
authors.lastname: Kartman
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001835:Body Weight; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000191:economics*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy* / Q000191:economics*; D007328:Insulin / Q000191:economics* / Q000627:therapeutic use*; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D017059:Models, Econometric; D015999:Multivariate Analysis; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human
keywords: HbA(1c); diabetes; insulin; weight