title: Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis.
abstract: BACKGROUND
  More intensive glycemic control reduces the risk of microvascular disease in patients with diabetes mellitus but has not been proven to reduce the risk of macrovascular events such as myocardial infarction and stroke. Poorer glycemic control, as indicated by glycated hemoglobin level concentration, is associated with an increased risk of heart failure (HF), but it is not known whether improved glycemic control reduces this risk. We conducted a meta-analysis of randomized controlled trials comparing strategies of more versus less intensive glucose-lowering that reported HF events.
  
  
  METHODS
  Two investigators independently searched PubMed, the Cochrane CENTRAL register of controlled trials, metaRegister, pre-MEDLINE, and CINAHL from January 1970 to October 2010 for prospective controlled randomized trials comparing a more intensive glucose-lowering regimen to a standard regimen. The outcome of interest was HF-related events (both fatal and nonfatal). Odds ratios (ORs) were calculated from published data from relevant trials and pooled with a random-effects meta-analysis.
  
  
  RESULTS
  A total of 37,229 patients from 8 randomized trials were included in the analysis. Follow-up ranged from 2.3 to 10.1 years, and the overall number of HF-related events was 1469 (55% in the intensive treatment arm). The mean difference in glycated hemoglobin level between patients given standard treatment and those allocated to a more intensive regimen was 0.9%. Overall, the risk of HF-related events did not differ significantly between intensive glycemic control and standard treatment (OR 1.20, 95% CI 0.96-1.48), but the effect estimate was highly heterogeneous (I(2) = 69%). At subgroup analysis, intensive glycemic control achieved with high thiazolidinediones use significantly increased HF risk (OR 1.33, 95% CI 1.02-1.72).
  
  
  CONCLUSIONS
  More intensive glycemic control in patients with type 2 diabetes mellitus did not reduce the occurrence of HF events. Furthermore, intensive glycemic control with thiazolidinediones increased the risk of HF. These findings question a direct mechanistic link between hyperglycemia and HF.
authors.affiliation: Cardiology Unit, Department of Internal Medicine, University of Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Castagno
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baird-Gunning
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.forename: Michael R
authors.initials: MR
authors.lastname: MacDonald
authors.forename: Mark C
authors.initials: MC
authors.lastname: Petrie
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Gaita
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones