title: Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care.
abstract: OBJECTIVE
  To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones).
  
  
  METHODS
  Open cohort study.
  
  
  METHODS
  1243 general practices contributing data to the QResearch database in England.
  
  
  METHODS
  469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015.
  
  
  METHODS
  Diabetes drugs (glitazones, gliptins, metformin, sulphonylureas, insulin, other) alone and in combination.
  
  
  METHODS
  First recorded diagnoses of cardiovascular disease, heart failure, and all cause mortality recorded on the patients' primary care, mortality, or hospital record. Cox proportional hazards models were used to estimate hazard ratios for diabetes treatments, adjusting for potential confounders.
  
  
  RESULTS
  During follow-up, 21 308 patients (4.5%) received prescriptions for glitazones and 32 533 (6.9%) received prescriptions for gliptins. Compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular disease; corresponding values for glitazones were significantly decreased risks of 23% for all cause mortality, 26% for heart failure, and 25% for cardiovascular disease. Compared with no current treatment, there were no significant associations between monotherapy with gliptins and risk of any complications. Dual treatment with gliptins and metformin was associated with a decreased risk of all three outcomes (reductions of 38% for heart failure, 33% for cardiovascular disease, and 48% for all cause mortality). Triple treatment with metformin, sulphonylureas, and gliptins was associated with a decreased risk of all three outcomes (reductions of 40% for heart failure, 30% for cardiovascular disease, and 51% for all cause mortality). Compared with no current treatment, monotherapy with glitazone was associated with a 50% decreased risk of heart failure, and dual treatment with glitazones and metformin was associated with a decreased risk of all three outcomes (reductions of 50% for heart failure, 54% for cardiovascular disease, and 45% for all cause mortality); dual treatment with glitazones and sulphonylureas was associated with risk reductions of 35% for heart failure and 25% for cardiovascular disease; triple treatment with metformin, sulphonylureas, and glitazones was associated with decreased risks of all three outcomes (reductions of 46% for heart failure, 41% for cardiovascular disease, and 56% for all cause mortality).
  
  
  CONCLUSIONS
  There are clinically important differences in risk of cardiovascular disease, heart failure, and all cause mortality between different diabetes drugs alone and in combination. Overall, use of gliptins or glitazones was associated with decreased risks of heart failure, cardiovascular disease, and all cause mortality compared with non-use of these drugs. These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, might have implications for prescribing of diabetes drugs.
authors.affiliation: Division of Primary Care, University Park, University of Nottingham, Nottingham NG2 7RD, UK Julia.hippisley-cox@nottingham.ac.uk.
authors.forename: Julia
authors.initials: J
authors.lastname: Hippisley-Cox
authors.affiliation: Division of Primary Care, University Park, University of Nottingham, Nottingham NG2 7RD, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Coupland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002423:Cause of Death; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004739:England; D005260:Female; D006333:Heart Failure / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009026:Mortality; D011320:Primary Health Care; D016016:Proportional Hazards Models; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin