title: Consequences of delaying treatment intensification in type 2 diabetes: evidence from a UK database.
abstract: Type 2 diabetes mellitus (TD2M) treatment focuses on achieving glycemic control, with HbA1c targeted at 6.5-7.5%. Clinicians commonly delay treatment intensification despite patients failing glycemic targets. This study evaluated longitudinal clinical and cost outcomes in patients failing metformin monotherapy using electronic medical records.
  
  
  
  Adults with incident T2DM were identified in the UK Clinical Practice Research Datalink (CPRD) from 1 January 2000 to 31 March 2014. Patients were initiated on metformin monotherapy but had not reached target (HbA1c <7%). Patients were grouped by time to intensification of second-line therapy from first recorded HbA1c ≥7%: Group A, rapid intensification within 365 days; Group B, delayed intensification days 366-1824; Group C, never intensified. Patients were followed from day 366 for 5 years until end of study, switch to insulin, migration or death.
  
  
  
  The study evaluated baseline clinical and medication characteristics which were re-evaluated each year, including HbA1c, weight, cholesterol and concomitant prescribing.
  
  
  
  A total of 6710 patients were included (Group A 2647, Group B 2452, Group C 1611). Group A achieved a significant decline in HbA1c at 1 year post-index date compared to Groups B and C (-1.13% Group A; +0.26% Group B, +0.16% Group C). A significantly higher proportion of patients achieved HbA1c target < 7% in Group A (Group A [45.8%]; Group B [19.1%], p < 0.0001). Using an adjusted hazard model, Group A was found to achieve the HbA1c target from the index date significantly faster than Group B (hazard ratio 3.25 [95% CI 2.87-3.69]). The most commonly prescribed second-line medications were sulfonylureas in Groups A and B throughout observation and were associated with significant weight gain (+1.3 kg per patient) in the adjusted models.
  
  
  
  Patients who were rapidly intensified achieved a maintained reduction in HbA1c faster than those with delayed intensification or no second-line therapy, despite a higher baseline HbA1c.
authors.affiliation: a Explore-Epi Ltd , Norfolk , UK ;
authors.forename: Louise
authors.initials: L
authors.lastname: Watson
authors.affiliation: b MSD UK , Hoddesdon , UK ;
authors.forename: Romita
authors.initials: R
authors.lastname: Das
authors.affiliation: a Explore-Epi Ltd , Norfolk , UK ;
authors.forename: Ruth
authors.initials: R
authors.lastname: Farquhar
authors.affiliation: b MSD UK , Hoddesdon , UK ;
authors.forename: Haya
authors.initials: H
authors.lastname: Langerman
authors.affiliation: c Diabetes and Endocrine Centre , Heart of England NHS Foundation Trust and University of Birmingham , UK.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Barnett
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D061665:Time-to-Treatment / Q000706:statistics & numerical data*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: Diabetes; epidemiology; hyperglycemia; intensification; metformin