title: Impact on glycated haemoglobin of a biological response-based measure of medication adherence.
abstract: OBJECTIVE
  The aim of this study was to examine the relationship between a specific glycated haemoglobin (HbA1c) measurement and a pharmaceutical dispensings-based measure of adherence calculated over the 90 days before each HbA1c measure among patients who have newly initiated metformin therapy.
  
  
  METHODS
  We identified 3109 people with type 2 diabetes who initiated metformin as their first-ever antihyperglycaemic drug, analysing all 9918 HbA1c measurements that were taken over the next 2 years. We used an adaptation of the 'proportion of days covered' method for assessing medication adherence that corresponded to an ∼90-day interval preceding an HbA1c measurement, terming the adaptation the 'biological response-based proportion of days covered' (BRB-PDC). To account for multiple observations per patient, we analysed the association between HbA1c and BRB-PDC within the generalized estimating equation framework. Analyses were stratified by HbA1c level before metformin initiation using a threshold of 8% (64 mmol/mol).
  
  
  RESULTS
  After multivariable adjustment using 0% adherence as the reference category, BRB-PDC in the range 50-79% was associated with HbA1c values lower by -0.113 [95% confidence interval (CI) -0.202, -0.025] among patients with pre-metformin HbA1c <8%, and by -0.247 (95% CI -0.390, -0.104) among those with HbA1c ≥8% at metformin initiation. Full adherence (≥80%) was associated with HbA1c values lower by -0.175% (95% CI -0.257, -0.093) and by -0.453% (95% CI -0.586, -0.320).
  
  
  CONCLUSIONS
  Using this novel short-interval approach that more closely associates adherence with the expected biological response, the association between better adherence and HbA1c levels was considerably stronger than has been previously reported; however, the strength of the impact was dependent upon the HbA1c level before initiating metformin.
authors.affiliation: Kaiser Permanente Center for Health Research, Portland, OR, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Nichols
authors.affiliation: Kaiser Permanente Center for Health Research, Portland, OR, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Rosales
authors.affiliation: Kaiser Permanente Center for Health Research, Portland, OR, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Kimes
authors.affiliation: Merck & Co, Inc., Kenilworth, NJ, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tunceli
authors.affiliation: Merck & Co, Inc., Kenilworth, NJ, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kurtyka
authors.affiliation: Merck & Co, Inc., Kenilworth, NJ, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mavros
authors.affiliation: Kaiser Permanente Institute for Health Research, Denver, CO, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Steiner
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis* / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016903:Drug Monitoring
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: glycaemic control; metformin; observational study; pharmaco-epidemiology