Sodium–glucose co-transporter 2 (SGLT2) inhibitors exert their actions within the kidneys, serving an important glucose-lowering effect in the treatment of diabetes mellitus. However, it is unclear if SGLT2 inhibitors can impact glucose sensitivity of skeletal muscle during short term administration. Goto et al. examined 20 individuals experiencing T2DM and their response to a single week’s treatment with empagliflozin, a common SGLT2 inhibitor. The study measured relevant metabolic outcomes following SGLT2 inhibition, including low and high density lipoproteins and urinary glucose levels. In addition, the work measured skeletal muscle mass, through body composition using bioimpedance. This experiment revealed that 1 week’s administration of empagliflozin significantly decreases body mass index as well as overall fat and skeletal muscle mass. Plasma glucose also demonstrated reduced levels, indicating a decline in insulin concentrations.

The authors suggest that SGLT2 inhibitor-associated elevation of glucose metabolism may occur through skeletal muscle mitochondrial metabolism and intramyocellular lipid mobilisation. Whilst much work remains to be done to fully appreciate the mechanism and implications of SGLT2 inhibition for specific tissues, these experiments demonstrate that short term exposure to SGLT2 can evoke substantial shifts in body composition, plasma glucose and skeletal muscle.

Read the full article in Endocrine Connections 9 599–606