Grant: Catalyst Grant: Musculoskeletal Health and Arthritis

A burn injury induces dramatic stress and metabolic responses leading to high blood sugar levels (hyperglycemia) that are associated with increased morbidity and mortality. In a recent clinical trial, we showed that controlling blood sugar levels using insulin improved post-burn infections, sepsis and morbidity. However, we, and others, have also shown that insulin therapy is associated with the risk of life-threatening low sugar levels (hypoglycemia), which in turn leads to profound post-burn complications. It would be ideal to achieve good blood sugar control but without the risk of adverse effects of low blood sugar associated with insulin. Metformin appears to be such an agent to control hyperglycemia safely and effectively. We recently conducted a single centre Phase II trial and found that metformin controls blood sugar well as insulin, but was not associated with the same risk of hypoglycemia. We also found that metformin limits other pathologic post-burn alterations, strongly suggesting that the administration of metformin is beneficial for the outcome of burn patients. We now propose to study metformin in a large Canadian-wide multi centre study to determine whether metformin can be implemented as standard-of-care in severely burned patients. Our hypothesis is that metformin will be as good as insulin at controlling blood sugar, but without the risk of hypoglycemia, and that it will limit other pathologic alterations post-burn to yield improvements in morbidity and mortality. The major burn centres in Canada will participate in the trial, and results from this study could improve the standard of burn care and health outcomes of burn patients world-wide.