title: Effects of intensive glucose lowering in treatment of type 2 diabetes mellitus on cardiovascular outcomes: A meta-analysis of data from 58,160 patients in 13 randomized controlled trials.
abstract: BACKGROUND
  Previous trials indicated that intensive glucose lowering in treatment of patients with type 2 diabetes mellitus (T2DM) was associated with a higher incidence of mortality. We therefore conducted a meta-analysis to evaluate the benefits and harms of intensive glucose lowering therapy in treatment of T2DM patients on major cardiovascular outcomes.
  
  
  METHODS
  Randomized controlled trials (RCTs) were obtained from searches of PubMed, EmBase, and the Cochrane Library electronic databases until Feb. 2016. Relative risk (RR) was used to measure the treatment effect by random-effect model. Meta-regression, sensitivity analyses, subgroup analyses, and publication biases were also conducted.
  
  
  RESULTS
  Thirteen RCTs were included with 58,160 T2DM patients and reported 5719 major cardiovascular events (MACEs), 6569 deaths, 2057 cardiac death cases, 3201 myocardial infarction (MI) cases, 1835 stroke cases, and 1778 congestive heart failure cases. Intensive glucose lowering therapy significantly reduced risk of MACEs (RR: 0.92; 95%CI: 0.85-1.00; P=0.042), and MI (RR: 0.90; 95%CI: 0.82-0.98; P=0.020) compared with conventional glucose control therapy. Furthermore, intensive glucose lowering therapy has no significant effect on the incidence of total mortality (RR: 0.98; 95%CI: 0.91-1.07; P=0.693), cardiac death (RR: 1.00; 95%CI: 0.87-1.04; P=0.999), stroke (RR: 0.94; 95%CI: 0.84-1.06; P=0.333), and congestive heart failure (RR: 1.19; 95%CI: 0.96-1.48; P=0.108).
  
  
  CONCLUSIONS
  T2DM patients who received intensive glucose lowering therapy are associated with a reduced risk of MACEs and MI, whereas it has no significant effect on the risk of total mortality, cardiac death, stroke, and congestive heart failure. These effects might differ when stratified by baseline characteristics in T2DM patients.
authors.affiliation: Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Fang
authors.affiliation: Department of Rehabilitation Institute, Shanghai Seventh People's Hospital, Shanghai 200137, China.
authors.forename: Yu-Hao
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng District, Beijing 100050, China.
authors.forename: Yong-Ji
authors.initials: YJ
authors.lastname: Tian
authors.affiliation: Department of Emergency, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng District, Beijing 100050, China.
authors.forename: Han-Yang
authors.initials: HY
authors.lastname: Du
authors.affiliation: Department of Anesthesiolgy, Beijing TongRen Hospital, Capital Medical University, No.2 Chongwenmennei Street, Dongcheng District, Beijing 100730, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: zhongliyong@126.com.
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Zhong
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents
keywords: Cardiovascular; Intensive glucose lowering; Meta-analysis; Type 2 diabetes mellitus