title: Effect of atorvastatin on glycaemia progression in patients with diabetes: an analysis from the Collaborative Atorvastatin in Diabetes Trial (CARDS).
abstract: OBJECTIVE
  In an individual-level analysis we examined the effect of atorvastatin on glycaemia progression in type 2 diabetes and whether glycaemia effects reduce the prevention of cardiovascular disease (CVD) with atorvastatin.
  
  
  METHODS
  The study population comprised 2,739 people taking part in the Collaborative Atorvastatin Diabetes Study (CARDS) who were randomised to receive atorvastatin 10 mg or placebo and who had post-randomisation HbA1c data. This secondary analysis used Cox regression to estimate the effect of atorvastatin on glycaemia progression, defined as an increase in HbA1c of ≥ 0.5% (5.5 mmol/mol) or intensification of diabetes therapy. Mixed models were used to estimate the effect of atorvastatin on HbA1c as a continuous endpoint.
  
  
  RESULTS
  Glycaemia progression occurred in 73.6% of participants allocated placebo and 78.1% of those allocated atorvastatin (HR 1.18 [95% CI 1.08, 1.29], p < 0.001) by the end of follow-up. The HR was 1.22 (95% CI 1.19, 1.35) in men and 1.11 (95% CI 0.95, 1.29) in women (p = 0.098 for the sex interaction). A similar effect was seen in on-treatment analyses: HR 1.20 (95% CI 1.07, 1.35), p = 0.001. The net mean treatment effect on HbA1c was 0.14% (95% CI 0.08, 0.21) (1.5 mmol/mol). The effect did not increase through time. Diabetes treatment intensification alone did not differ with statin allocation. Neither baseline nor 1-year-attained HbA1c predicted subsequent CVD, and the atorvastatin effect on CVD did not vary by HbA1c change (interaction p value 0.229).
  
  
  CONCLUSIONS
  The effect of atorvastatin 10 mg on glycaemia progression among those with diabetes is statistically significant but very small, is not significantly different between sexes, does not increase with duration of statin and does not have an impact on the magnitude of CVD risk reduction with atorvastatin.
authors.affiliation: Diabetes Epidemiology Unit, Division of Population Health Sciences, University of Dundee, The Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, Scotland, UK.
authors.forename: Shona J
authors.initials: SJ
authors.lastname: Livingstone
authors.affiliation: Diabetes Epidemiology Unit, Division of Population Health Sciences, University of Dundee, The Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, Scotland, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Looker
authors.affiliation: Diabetes Epidemiology Unit, Division of Population Health Sciences, University of Dundee, The Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, Scotland, UK.
authors.forename: Tahira
authors.initials: T
authors.lastname: Akbar
authors.affiliation: Department of Endocrinology and Diabetes, University College Hospital, London, UK.
authors.forename: D John
authors.initials: DJ
authors.lastname: Betteridge
authors.affiliation: Cardiovascular Research Group, School of Biosciences, University of Manchester, Manchester, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durrington
authors.affiliation: Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
authors.forename: H Andrew W
authors.initials: HA
authors.lastname: Neil
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Fuller
authors.affiliation: Diabetes Epidemiology Unit, Division of Population Health Sciences, University of Dundee, The Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, Scotland, UK. h.colhoun@dundee.ac.uk.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D006113:United Kingdom
chemical_list: D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Atorvastatin; Cardiovascular disease; Glycaemia; HbA1c