title: Glucose Control in Severely Burned Patients Using Metformin: An Interim Safety and Efficacy Analysis of a Phase II Randomized Controlled Trial.
abstract: OBJECTIVE
  To determine whether metformin can achieve glucose control no worse than insulin (noninferiority) without the danger of hypoglycemia (superiority). In addition, to assess whether metformin has any additional effects on lipolysis and inflammation that will enhance burn recovery (superiority).
  
  
  BACKGROUND
  Hyperglycemia and insulin resistance after burn injury are associated with increased morbidity and mortality. Insulin administration improves postburn infections, severity of sepsis, and morbidity, but also causes a 4-5-fold increase in hypoglycemia, which is associated with a 9-fold increase in mortality.
  
  
  METHODS
  Severely burned adult patients with burns over 20% total body surface area (TBSA) burn were prospectively randomized in this Phase II clinical trial to either metformin or insulin (standard of care) treatment. Primary outcomes were glucose levels and incidence of hypoglycemia. Secondary outcomes included glucose and fat metabolism, and clinical outcomes.
  
  
  RESULTS
  Forty-four patients were enrolled in this Phase II clinical trial, 18 metformin and 26 insulin patients. Demographics, burn size, concomitant injuries, and mortality were comparable between both groups. Metformin controlled blood glucose as equally as insulin with no difference between the 2 treatment groups, P > 0.05. While there was a 15% incidence of hypoglycemia in the insulin group, there was only 1 mild hypoglycemic episode (6%) in the metformin group, P < 0.05. Oral glucose tolerance tests at discharge revealed that metformin significantly improved insulin sensitivity, P < 0.05. Furthermore, metformin had a strong antilipolytic effect after burn injury when compared with insulin and was associated with significantly reduced inflammation, P < 0.05.
  
  
  CONCLUSIONS
  Metformin decreases glucose equally as effective as insulin without causing hypoglycemia, with additional benefits including improved insulin resistance and decreased endogenous insulin synthesis when compared with insulin controls. These results indicate that metformin is safe in burn patients and further supports the use of metformin in severely burned patients for postburn control of hyperglycemia and insulin resistance.
authors.affiliation: *Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada †Sunnybrook Research Institute, Toronto, Ontario, Canada ‡Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada §Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
authors.forename: Abdikarim
authors.initials: A
authors.lastname: Abdullahi
authors.forename: Marjorie
authors.initials: M
authors.lastname: Burnett
authors.forename: Sarah
authors.initials: S
authors.lastname: Rehou
authors.forename: Mile
authors.initials: M
authors.lastname: Stanojcic
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D002056:Burns / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D005223:Fats / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D005223:Fats; D007328:Insulin; D008055:Lipids; D008687:Metformin