title: Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: ADVANCE-ON.
abstract: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Here, we examine the long-term effects of intensive glucose control on risk of ESKD and other outcomes.
  
  
  
  Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes.
  
  
  
  A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P < 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P > 0.26).
  
  
  
  Intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Muh Geot
authors.initials: MG
authors.lastname: Wong
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia vperkovic@georgeinstitute.org.au.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia The George Institute for Global Health, University of Oxford, Oxford, U.K. Department of Epidemiology, Johns Hopkins University, Baltimore, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.affiliation: Centre hospitalier de l`Universite de Montreal, Montreal, Canada.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.affiliation: Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harrap
authors.affiliation: University of Sheffield and Sheffield Teaching Hospitals, National Health Service Foundation Trust, Sheffield, U.K.
authors.forename: Simon
authors.initials: S
authors.lastname: Heller
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia The George Institute for Global Health, University of Oxford, Oxford, U.K.
authors.forename: Stephen
authors.initials: S
authors.lastname: MacMahon
authors.affiliation: Policlinico di Monza and IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.affiliation: Hôpital Bichat-Claude Bernard and Université Paris 7, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
authors.forename: David
authors.initials: D
authors.lastname: Matthews
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, U.K.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, U.K.
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
authors.affiliation: Institute of Cardiovascular Science, University College, London, U.K.
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, Australia School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia szoungas@georgeinstitute.org.au.
authors.forename: Sophia
authors.initials: S
authors.lastname: Zoungas
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005907:Gliclazide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007190:Indapamide / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000097:blood / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D004338:Drug Combinations; D005907:Gliclazide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007190:Indapamide; D020913:Perindopril; C494243:indapamide, perindopril drug combination