title: Effects on All-cause Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes by Comparing Insulin With Oral Hypoglycemic Agent Therapy: A Meta-analysis of Randomized Controlled Trials.
abstract: OBJECTIVE
  Retrospective, case-control studies and prospective randomized controlled trials (RCTs) on insulin treatment for diabetic patients yielded contradictory mortality and cardiovascular outcomes. We aimed to evaluate the effects of insulin versus oral hypoglycemic agents (OHAs) on all-cause mortality and cardiovascular outcomes in patients with type 2 diabetes (T2D).
  
  
  METHODS
  We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Chinese Technical Periodicals, and Wanfang Data, up to July 10, 2015, for RCTs on insulin and OHAs that assessed all-cause mortality and/or cardiovascular death as primary end points. We derived pooled risk ratios (RRs) as summary statistics.
  
  
  RESULTS
  Three trials were included in which 7649 patients received insulin and 8322 received OHAs, with mean (SD) diabetes duration of 5.0 (6.2) and 4.4 (5.9) years, respectively. Insulin did not differ from OHAs in all-cause mortality (RR = 1.00; 95% CI, 0.93-1.07), cardiovascular death (RR = 1.00; 95% CI, 0.91-1.09), myocardial infarction (RR = 1.04; 95% CI, 0.93-1.16), angina (RR = 0.97; 95% CI, 0.88-1.06), sudden death (RR = 1.02; 95% CI, 0.66-1.56), or stroke (RR = 1.01; 95% CI, 0.88-1.15). Insulin reduced the risk of heart failure compared with OHAs (RR = 0.87; 95% CI, 0.75-0.99). In the subgroup of secondary prevention of cardiovascular diseases (CVDs) or very high risk of CVDs, insulin did not differ from OHAs in all-cause mortality (RR = 0.99; 95% CI, 0.92-1.07), cardiovascular death (RR = 0.99; 95% CI, 0.90-1.09), myocardial infarction (RR = 1.01; 95% CI, 0.88-1.15), heart failure (RR = 0.69; 95% CI, 0.34-1.40), or stroke (RR = 1.05; 95% CI, 0.90-1.21).
  
  
  CONCLUSIONS
  Insulin did not provide a clear benefit over OHAs in all-cause mortality or cardiovascular outcomes in the patients with T2D. Insulin therapy has many shortcomings, including inconvenience (injection, strict blood glucose monitoring), hypoglycemia, and obvious weight gain. Thus, we conclude that no robust evidence supports the active use of insulin for this population at present.
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Xi׳an No. 4 Hospital, Xi׳an, China.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China. Electronic address: buddyjun@hotmail.com.
authors.forename: Nanwei
authors.initials: N
authors.lastname: Tong
mesh_terms: D000787:Angina Pectoris / Q000453:epidemiology; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: all-cause mortality; cardiovascular outcomes; insulin; oral hypoglycemic agent; type 2 diabetes