title: Diabetes treatment intensification and associated changes in HbA1c and body mass index: a cohort study.
abstract: BACKGROUND
  To describe common type 2 diabetes treatment intensification regimens, patients' characteristics and changes in glycated hemoglobin (HbA1c) and body mass index (BMI).
  
  
  METHODS
  We constructed a national retrospective cohort of veterans initially treated for diabetes with either metformin or sulfonylurea from 2001 through 2008, using Veterans Health Administration (VHA) and Medicare data. Patients were followed through September, 2011 to identify common diabetes treatment intensification regimens. We evaluated changes in HbA1c and BMI post-intensification for metformin-based regimens.
  
  
  RESULTS
  We identified 323,857 veterans who initiated diabetes treatment. Of these, 55 % initiated metformin, 43 % sulfonylurea and 2 % other regimens. Fifty percent (N = 89,057) of metformin initiators remained on metformin monotherapy over a median follow-up 58 months (interquartile range [IQR] 35, 74). Among 80,725 patients who intensified metformin monotherapy, the four most common regimens were addition of sulfonylurea (79 %), thiazolidinedione [TZD] (6 %), or insulin (8 %), and switch to insulin monotherapy (2 %). Across these regimens, median HbA1c values declined from a range of 7.0-7.8 % (53-62 mmol/mol) at intensification to 6.6-7.0 % (49-53 mmol/mol) at 1 year, and remained stable up to 3 years afterwards. Median BMI ranged between 30.5 and 32 kg/m(2) at intensification and increased very modestly in those who intensified with oral regimens, but 1-2 kg/m(2) over 3 years among those who intensified with insulin-based regimens.
  
  
  CONCLUSIONS
  By 1 year post-intensification of metformin monotherapy, HbA1c declined in all four common intensification regimens, and remained close to 7 % in subsequent follow-up. BMI increased substantially for those on insulin-based regimens.
authors.affiliation: Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA. christianne.roumie@vanderbilt.edu.|Department of Medicine, Vanderbilt University, Nashville, TN, USA. christianne.roumie@vanderbilt.edu.|Nashville VA Medical Center, 1310 24th Ave South GRECC, Nashville, TN, 37212, USA. christianne.roumie@vanderbilt.edu.
authors.forename: Christianne L
authors.initials: CL
authors.lastname: Roumie
authors.affiliation: Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA.|Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Greevy
authors.affiliation: Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA.|Department of Health Policy, Vanderbilt University, Nashville, TN, USA.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.affiliation: Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA.|Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.affiliation: Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA.|Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Xulei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D Center, Nashville, TN, USA.|Department of Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Health Policy, Vanderbilt University, Nashville, TN, USA.
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
mesh_terms: D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C089946:2,4-thiazolidinedione
keywords: Adherence; Clinical effectiveness, treatment intensification; Clinical outcomes; Diabetes mellitus type 2; Patterns of care