title: Comparative cardiovascular morbidity and mortality in patients taking different insulin regimens for type 2 diabetes: a systematic review.
abstract: OBJECTIVE
  To summarise the literature evaluating the association between different insulin regimens and the incidence of cardiovascular morbidity and mortality in adults with type 2 diabetes.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Multiple biomedical databases (The Cochrane Library, PubMed, EMBASE, and International Pharmaceutical Abstracts) were searched from their inception to February 2014. References of included studies were hand searched. Randomised controlled trials (RCTs), cohort studies or case-control studies examining adults (≥18 years) with type 2 diabetes taking any type, dose and/or regimen of insulin were eligible for inclusion in this review.
  
  
  METHODS
  Primary outcomes were cardiovascular morbidity and mortality including fatal and/or non-fatal myocardial infarction, fatal and/or non-fatal stroke, major adverse cardiac events and cardiovascular death. All-cause mortality was assessed as a secondary outcome.
  
  
  RESULTS
  Of the 3122 studies identified, 2 RCTs and 6 cohort studies were selected. No case-control studies met the inclusion criteria. The studies examined a total of 109,910 patients. Quantitative synthesis of the results from included studies was not possible due to a large amount of clinical heterogeneity. Each study evaluated cardiovascular outcomes across different insulin-exposure contrasts. RCTs did not identify any difference in cardiovascular risks among a fixed versus variable insulin regimen, or a prandial versus basal regimen, albeit clinically important risks and benefits cannot be ruled out due to wide CIs. Findings from cohort studies were variable with an increased and decreased risk of cardiovascular events and all-cause mortality being reported.
  
  
  CONCLUSIONS
  This systematic review of randomised and non-randomised studies identifies a substantive gap in the literature surrounding the cardiovascular morbidity and mortality of patients using different regimens of insulin. There is a need for more consistent high-quality evidence investigating the impact of insulin use on cardiovascular outcomes in patients with type 2 diabetes.
  
  
  BACKGROUND
  
  CRD42014007631.
authors.affiliation: School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Hilary I
authors.initials: HI
authors.lastname: Price
authors.affiliation: School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Meghan D
authors.initials: MD
authors.lastname: Agnew
authors.affiliation: School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Gamble
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: cardiovascular outcomes; insulin; systematic review; type 2 diabetes