title: Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes.
abstract: To analyse time to cardiovascular events and mortality in patients with type 2 diabetes (T2D) who received treatment intensification with insulin or a glucagon-like peptide-1 (GLP-1ar) analogue following dual therapy failure with metformin (MET) and sulphonylurea (SU).
  
  
  
  A retrospective cohort study was conducted in 2003 patients who were newly treated with a GLP-1ar or insulin following dual therapy (MET+SU) failure between 2006 and 2014. Data were sourced from The Health Improvement Network database. Risks of major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke and all-cause mortality) were compared between MET+SU+insulin (N=1584) versus MET+SU+GLP-1ar (N=419). Follow-up was for 5 years (6614 person-years). Propensity score matching analysis and Cox proportional hazard models were employed.
  
  
  
  Mean age was 52.8±14.1 years. Overall, the number of MACE was 231 vs 11 for patients who added insulin versus GLP-1ar, respectively (44.5 vs 7.7 per 1000-person-years adjusted HR (aHR): 0.27; 95% CI 0.14 to 0.53; p<0.0001). Insulin was associated with significant increase in weight compared with GLP-1ar (1.78 vs -3.93 kg; p<0.0001) but haemoglobin A1c reduction was similar between both treatment groups (-1.29 vs -0.98; p=0.156). In a subgroup analysis of obese patients (body mass index >30 kg/m(2)) there were 84 vs 11 composite outcomes (38.6 vs 8.1 per 1000 person-years; aHR: 0.31; 95% CI 0.16 to 0.61; p=0.001) in the insulin and GLP-1ar groups, respectively.
  
  
  
  In this cohort of obese people with T2DM, intensification of dual oral therapy by adding GLP-1ar analogue is associated with a lower MACE outcome in routine clinical practice, compared with adding insulin therapy as the third glucose-lowering agent.
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Uchenna
authors.initials: U
authors.lastname: Anyanwagu
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Jil
authors.initials: J
authors.lastname: Mamza
authors.affiliation: Research Design Services (East Midlands), School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Rajnikant
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Donnelly
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Iskandar
authors.initials: I
authors.lastname: Idris
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D002423:Cause of Death; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000401:mortality; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human