Beyond diabetes: harnessing the power of metformin in burn care

Burn injuries are complex and devastating traumas that trigger a profound systemic metabolic response, characterized by hyperglycemia, insulin resistance, and a hypermetabolic state. Notably, hyperglycemia is a critical determinant of worse prognoses in burn patients. While insulin has long been the gold standard for managing post-burn hyperglycemia, its therapy is associated with a risk of hypoglycemic events, which can exacerbate morbidity and compromise patient outcomes. As such, investigation of alternative therapeutics is warranted to improve glycemic control while mitigating associated risks. Recently, metformin, a first-line therapy for the treatment of type II diabetes, has emerged as a potential therapeutic agent for the management of post-burn hyperglycemia as well as other burn injury sequelae. This review examines the mechanistic underpinnings of metformin, its potential application in managing post-burn hyperglycemia, and its comparative advantages over other hypoglycemic agents. Additionally, we examine the broad spectrum of metformin's pleiotropic effects in the context of burn injury-extending beyond glycemic control to include attenuation of muscle catabolism, suppression of lipolysis, regulation of non-shivering thermogenesis, support of mitochondrial and immune function, enhanced wound healing, and its potential role in addressing burn-induced acceleration of biological aging. Taken together, we discuss how metformin represents a paradigm shift in burn care, with the potential to substantially improve patient outcomes.