Metformin Blunts Stress-Induced Hyperglycemia after Thermal Injury

Abstract

Hyperglycemia is associated with detriments in immune function and impaired wound healing. The purpose of this study was to assess the effect of metformin, an oral antihyperglycemic agent approved for patients with diabetes mellitus, on glucose metabolism in severely burned patients.

Metformin was given in a double-blind, placebo-controlled fashion to 10 patients, all with burns > 60% body surface area (age, 36 ± 4 years; weight, 92 ± 3 kg; mean ± SEM). After 8 days of metformin or placebo, glucose kinetics were quantitated using isotopic dilution with 6,6-d2 glucose and indirect calorimetry. Measurements were made during fasting; during an intravenous glucose infusion (30 μmol/kg/min); and during a hyperinsulinemic (500 mIU/m2/h), euglycemic clamp (mean plasma glucose concentration, 6.5 ± 0.3 mmol/L).

During fasting, metformin-treated subjects had a significantly lower rate of endogenous glucose production (met. 9.6) and glucose oxidation than placebo control subjects. With the administration of intravenous glucose, metformin treatment significantly accelerated glucose clearance, thereby attenuating hyperglycemia. During hyperinsulinemia, glucose uptake was significantly greater in metformin-treated patients. Patients receiving metformin also had a significantly higher plasma concentration of insulin.

These findings suggest a potential clinical efficacy of metformin to reduce stress-induced hyperglycemia by increasing glucose clearance. This effect may be mediated by either a metformin-induced augmentation of insulin sensitivity or by increasing insulin availability.