title: Effect of Intensive Versus Standard Blood Glucose Control in Patients With Type 2 Diabetes Mellitus in Different Regions of the World: Systematic Review and Meta-analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Regional variation in type 2 diabetes mellitus care may affect outcomes in patients treated with intensive versus standard blood glucose control. We sought to evaluate these differences between North America and the rest of the world.
  
  
  RESULTS
  Databases were searched from their inception through December 2013. Randomized controlled trials comparing the effects of intensive therapy with standard therapy for macro- and microvascular complications in adults with type 2 diabetes mellitus were selected. We calculated summary odds ratios (ORs) and 95% CIs with the random-effects model. The analysis included 34 967 patients from 17 randomized controlled trials (7 in North America and 10 in the rest of the world). There were no significant differences between intensive and standard therapy groups for all-cause mortality (OR 1.03, 95% CI 0.93 to 1.13) and cardiovascular mortality (OR 1.09, 95% CI 0.90 to 1.32). For trials conducted in North America, intensive therapy compared with standard glycemic control resulted in significantly higher all-cause mortality (OR 1.21, 95% CI 1.05 to 1.40) and cardiovascular mortality (OR 1.41, 95% CI 1.05 to 1.90) than trials conducted in the rest of the world (all-cause mortality OR 0.93, 95% CI 0.85 to 1.03; interaction P=0.006; cardiovascular mortality OR 0.89, 95% CI, 0.79 to 1.00; interaction P=0.007). Analysis of individual macro- and microvascular outcomes revealed no significant regional differences; however, the risk of severe hypoglycemia was significantly higher in trials of intensive therapy in North America (OR 3.52, 95% CI 3.07 to 4.03) compared with the rest of the world (OR 1.45, 95% CI 0.85 to 2.47; interaction P=0.001).
  
  
  CONCLUSIONS
  Randomization to intensive glycemic control in type 2 diabetes mellitus patients was associated with increases in all-cause mortality, cardiovascular mortality, and severe hypoglycemia in North America compared with the rest of the world. Further investigation into the pathobiology or patient variability underlying these findings is warranted.
authors.affiliation: Division of Cardiovascular Medicine, University of Utah, Salt Lake City, UT (P.S.).
authors.forename: Partha
authors.initials: P
authors.lastname: Sardar
authors.affiliation: Cardiovascular Division, Department of Medicine, Women's College Hospital, University of Toronto, Ontario, Canada (J.A.U.) Peter Munk Centre of Excellence in Multinational Clinical Trials, University Health Network, Heart & Stroke Richard Lewar Centre of Excellence, University of Toronto, Ontario, Canada (J.A.U., M.E.F.).
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Udell
authors.affiliation: Division of Cardiovascular Diseases, St. Luke's-Roosevelt Hospital Center of the Mount Sinai Health System, New York, NY (S.C.).
authors.forename: Saurav
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Cardiovascular Institute, The Mount Sinai Medical Center, New York, NY (S.B.).
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.affiliation: Division of Cardiovascular Diseases, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX (D.M.).
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukherjee
authors.affiliation: Peter Munk Centre of Excellence in Multinational Clinical Trials, University Health Network, Heart & Stroke Richard Lewar Centre of Excellence, University of Toronto, Ontario, Canada (J.A.U., M.E.F.).
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000401:mortality*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000401:mortality; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009656:North America; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents
keywords: cardiovascular mortality; diabetes mellitus; intensive glycemic control