title: Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials.
abstract: OBJECTIVE
  To determine all cause mortality and deaths from cardiovascular events related to intensive glucose lowering treatment in people with type 2 diabetes.
  
  
  METHODS
  Meta-analysis of randomised controlled trials.
  
  
  METHODS
  Medline, Embase, and the Cochrane database of systematic reviews.
  
  
  METHODS
  Randomised controlled trials that assessed the effect of intensive glucose lowering treatment on cardiovascular events and microvascular complications in adults (≥ 18 years) with type 2 diabetes.
  
  
  METHODS
  Primary end points were all cause mortality and death from cardiovascular causes. Secondary end points were severe hypoglycaemia and macrovascular and microvascular events. Synthesis of results Results are reported as risk ratios with 99% confidence intervals. Statistical heterogeneity between trials was assessed with χ(2), τ(2), and I(2) statistics. A fixed effect model was used to assess the effect on the outcomes of intensive glucose lowering versus standard treatment. The quality of clinical trials was assessed by the Jadad score.
  
  
  RESULTS
  13 studies were included. Of 34,533 patients, 18,315 received intensive glucose lowering treatment and 16,218 standard treatment. Intensive treatment did not significantly affect all cause mortality (risk ratio 1.04, 99% confidence interval 0.91 to 1.19) or cardiovascular death (1.11, 0.86 to 1.43). Intensive therapy was, however, associated with reductions in the risk of non-fatal myocardial infarction (0.85, 0.74 to 0.96, P<0.001), and microalbuminuria (0.90, 0.85 to 0.96, P<0.001) but a more than twofold increase in the risk of severe hypoglycaemia (2.33, 21.62 to 3.36, P<0.001). Over a treatment period of five years, 117 to 150 patients would need to be treated to avoid one myocardial infarction and 32 to 142 patients to avoid one episode of microalbuminuria, whereas one severe episode of hypoglycaemia would occur for every 15 to 52 patients. In analysis restricted to high quality studies (Jadad score >3), intensive treatment was not associated with any significant risk of reductions but resulted in a 47% increase in risk of congestive heart failure (P<0.001).
  
  
  CONCLUSIONS
  The overall results of this meta-analysis show limited benefits of intensive glucose lowering treatment on all cause mortality and deaths from cardiovascular causes. We cannot exclude a 9% reduction or a 19% increase in all cause mortality and a 14% reduction or a 43% increase in cardiovascular death. The benefit:risk ratio of intensive glucose lowering treatment in the prevention of macrovascular and microvascular events remains uncertain. The harm associated with severe hypoglycaemia might counterbalance the potential benefit of intensive glucose lowering treatment. More double blind randomised controlled trials are needed to establish the best therapeutic approach in people with type 2 diabetes.
authors.affiliation: Department of General Medicine, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Boussageon
authors.forename: Theodora
authors.initials: T
authors.lastname: Bejan-Angoulvant
authors.forename: Mitra
authors.initials: M
authors.lastname: Saadatian-Elahi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lafont
authors.forename: Claire
authors.initials: C
authors.lastname: Bergeonneau
authors.forename: Behrouz
authors.initials: B
authors.lastname: Kassaï
authors.forename: Sylvie
authors.initials: S
authors.lastname: Erpeldinger
authors.forename: James M
authors.initials: JM
authors.lastname: Wright
authors.forename: François
authors.initials: F
authors.lastname: Gueyffier
authors.forename: Catherine
authors.initials: C
authors.lastname: Cornu
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000401:mortality; D001786:Blood Glucose / Q000378:metabolism*; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D040242:Risk Reduction Behavior; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents