Influence of metformin on glucose intolerance and muscle catabolism following severe burn injury.
BACKGROUND
Hyperglycemia and accelerated muscle catabolism have been shown to adversely affect immune response and survival. The purpose of this study was to determine the effect of metformin on glucose kinetics and muscle protein metabolism in severely burned patients and assess any potential benefit of metformin in this clinical setting.


METHODS
In a double-blind, randomized manner, 8 adult burn patients received metformin (850 mg every 8 hours x 7 days), while 5 burn patients received placebo. Infusions of 6,6d2 glucose, d5 phenylalanine, sequential muscle biopsies, and femoral arterial, venous blood sampling allowed determination of glucose and muscle protein kinetics. Measurements were obtained immediately prior and at the conclusion of 7 days of treatment (metformin versus placebo). All patients received enteral feeds of comparable amounts during study.


RESULTS
Patients receiving metformin had a significant decrease in their plasma glucose concentration, the rate of glucose production, and an increase in glucose clearance. Metformin administration was also associated with a significant increase in the fractional synthetic rate of muscle protein and improvement in net muscle protein balance. Glucose kinetics and muscle protein metabolism were not significantly altered in the patients receiving placebo.


CONCLUSIONS
Metformin attenuates hyperglycemia and increases muscle protein synthesis in severely burned patients, thereby indicating a metabolic link between hyperglycemia and muscle loss following severe injury. Therefore, therapies that improve glucose tolerance such as metformin may be of clinical value in ameliorating muscle catabolism in critically injured patients.
Gore
Dennis C
DC
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555-1172, USA. dcgore@utmb.edu
Wolf
Steven E
SE
Sanford
Arthur
A
Herndon
David N
DN
Wolfe
Robert R
RR
D000328:Adult; D002056:Burns / Q000378:metabolism*; D002153:Calorimetry, Indirect; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*
D007004:Hypoglycemic Agents; D009124:Muscle Proteins; D008687:Metformin