title: Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes.
abstract: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes.
  
  
  
  We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1ctarget ≤6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment.
  
  
  
  Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] <100) and 1% had a small ARR (<0.5%, NNTB5>200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] <100) and 29% had a small ARI (NNTH5>200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients.
  
  
  
  Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified.
  
  
  
  ClinicalTrials.gov NCT00145925.
authors: Department of Vascular Medicine, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, the Netherlands.
authors: Joep
authors: J
authors: van der Leeuw
authors: Department of Vascular Medicine, University Medical Centre Utrecht, PO Box 85500, 3508 GA, Utrecht, the Netherlands. f.l.j.visseren@umcutrecht.nl.
authors: Frank L J
authors: FL
authors: Visseren
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.|The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors: Mark
authors: M
authors: Woodward
authors: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors: Yolanda
authors: Y
authors: van der Graaf
authors: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors: Diederick E
authors: DE
authors: Grobbee
authors: The Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors: Stephen
authors: S
authors: Harrap
authors: University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors: Simon
authors: S
authors: Heller
authors: Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy.
authors: Giuseppe
authors: G
authors: Mancia
authors: Hôpital Bichat-Claude Bernard and Université Paris 7, Paris, France.
authors: Michel
authors: M
authors: Marre
authors: International Centre for Circulatory Health, Imperial College, London, UK.
authors: Neil
authors: N
authors: Poulter
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: Sophia
authors: S
authors: Zoungas
authors: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors: John
authors: J
authors: Chalmers
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D005907:Gliclazide / Q000009:adverse effects / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007190:Indapamide / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000009:adverse effects / Q000627:therapeutic use; D057285:Precision Medicine / Q000379:methods*; D012307:Risk Factors; D040242:Risk Reduction Behavior
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D005907:Gliclazide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007190:Indapamide; D020913:Perindopril; C494243:indapamide, perindopril drug combination
keywords: Glycaemic target; Hypoglycaemia; Net benefit; Personalised medicine; Type 2 diabetes; Vascular complications