title: Mortality in Individuals Treated With Glucose-Lowering Agents: A Large, Controlled Cohort Study.
abstract: BACKGROUND
  Several observational studies and meta-analyses have reported increased mortality of patients taking sulfonylurea and insulin. The impact of patient profiles and concomitant therapies often remains unclear.
  
  
  OBJECTIVE
  The objective of the study was to quantify survival of patients after starting glucose-lowering agents (GLAs) and compare it with control subjects, matched for risk profiles and concomitant therapies.
  
  
  METHODS
  This was a retrospective, controlled, cohort study.
  
  
  METHODS
  The study is based on health expenditure records of the largest Belgian health mutual insurer, covering more than 4.4 million people.
  
  
  METHODS
  A total of 115 896 patients starting metformin, sulfonylurea, or insulin (alone or in combination) between January 2003 and December 2007 participated in the study. Control subjects without GLA therapy were matched for age, gender, history of cardiovascular events, and therapy with antihypertensives, statins and blood platelet aggregation inhibitors.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  Five-year survival after the start of GLA was measured.
  
  
  RESULTS
  Profiles of patients using different GLAs varied, with patients on sulfonylurea being oldest and patients on insulin having more frequently a history of cardiovascular disease. Excess mortality differed across GLA therapies compared with matched controls without GLAs, even after adjusting for observable characteristics. Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks. Age and concomitant use of statins strongly affect survival.
  
  
  CONCLUSIONS
  Differences exist in 5-year survival of patients on GLA, at least partly driven by the risk profile of the individuals themselves. Metformin use was associated with lowest 5-year mortality risk and statins dramatically lowered 5-year mortality throughout all cohorts.
authors.affiliation: STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Claesen
authors.affiliation: STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Gillard
authors.affiliation: STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: De Smet
authors.affiliation: STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Callens
authors.affiliation: STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: De Moor
authors.affiliation: STADIUS Center for Dynamical Systems (M.Cl., B.D.M.), Signal Processing and Data Analytics, Department of Electrical Engineering, iMinds Medical IT, (M.Cl., B.D.M.), and Department of Public Health and Primary Care (F.D.S.), KU Leuven, B-3000 Leuven, Belgium; Department of Clinical and Experimental Medicine (P.G., C.M.), University of Leuven-KUL and University Hospitals Leuven, B-3000 Leuven, Belgium; and Department of Medical Management (F.D.S., M.Ca.), National Alliance of Christian Mutualities, B-1090 Brussels, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001530:Belgium / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000150:complications / Q000401:mortality; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000401:mortality*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009026:Mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin