title: Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes.
abstract: BACKGROUND
  The aim of the study was to evaluate the effect of delay in treatment intensification (IT; clinical inertia) in conjunction with glycaemic burden on the risk of macrovascular events (CVE) in type 2 diabetes (T2DM) patients.
  
  
  METHODS
  A retrospective cohort study was carried out using United Kingdom Clinical Practice Research Datalink, including T2DM patients diagnosed from 1990 with follow-up data available until 2012.
  
  
  RESULTS
  In the cohort of 105,477 patients mean HbA1c was 8.1% (65 mmol/mol) at diagnosis, 11% had a history of cardiovascular disease, and 7.1% experienced at least one CVE during 5.3 years of median follow-up. In patients with HbA1c consistently above 7/7.5% (53/58 mmol/mol, n = 23,101/11,281) during 2 years post diagnosis, 26/22% never received any IT. Compared to patients with HbA1c <7% (<53 mmol/mol), in patients with HbA1c ≥7% (≥53 mmol/mol), a 1 year delay in receiving IT was associated with significantly increased risk of MI, stroke, HF and composite CVE by 67% (HR CI: 1.39, 2.01), 51% (HR CI: 1.25, 1.83), 64% (HR CI: 1.40, 1.91) and 62% (HR CI: 1.46, 1.80) respectively. One year delay in IT in interaction with HbA1c above 7.5% (58 mmol/mol) was also associated with similar increased risk of CVE.
  
  
  CONCLUSIONS
  Among patients with newly diagnosed T2DM, 22% remained under poor glycaemic control over 2 years, and 26% never received IT. Delay in IT by 1 year in conjunction with poor glycaemic control significantly increased the risk of MI, HF, stroke and composite CVE.
authors.affiliation: Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia. Sanjoy.Paul@qimrberghofer.edu.au.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Paul
authors.affiliation: Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia. kerenaftali.klein@qimrberghofer.edu.au.
authors.forename: Kerenaftali
authors.initials: K
authors.lastname: Klein
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej, Denmark. bltt@novonordisk.com.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Thorsted
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej, Denmark. mlwo@novonordisk.com.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wolden
authors.affiliation: Leicester Diabetes Centre, University of Leicester, Leicester, UK. kk22@le.ac.uk.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Khunti
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011314:Preventive Health Services; D011320:Primary Health Care; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human