title: Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
abstract: OBJECTIVE
  To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus.
  
  
  METHODS
  A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
  
  
  METHODS
  The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013.
  
  
  METHODS
  Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included.
  
  
  METHODS
  Two authors independently assessed studies for inclusion and extracted data.
  
  
  RESULTS
  18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate.
  
  
  CONCLUSIONS
  There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control.
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Kähler
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Berit
authors.initials: B
authors.lastname: Grevstad
authors.affiliation: Department of Medicine F, Gentofte Hospital, Gentofte, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Almdal
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.forename: Søren Søgaard
authors.initials: SS
authors.lastname: Lund
authors.affiliation: Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Bianca
authors.initials: B
authors.lastname: Hemmingsen
mesh_terms: D001786:Blood Glucose; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D007003:Hypoglycemia / Q000097:blood* / Q000150:complications; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents