Glutathione, or (GSH), is the primary intracellular antioxidant involved in preventing lipid and protein oxidation, and is a critical component in the enzymatic process used to detoxify hydroxide peroxide (H2O2)
A recent JAMA study in adults without diabetes showed only 24.5% remained on therapy at 12 months
These findings suggest melatonin enhances the antioxidant response and supports mitochondrial function under oxidative stress
However, metformin has been shown to enhance the translocation of GLUT2 to the apical membrane of enterocytes (Ait-Omar et al., 2011), providing a potential mechanism for the release of glucose from enterocytes into the intestinal lumen in response to metformin treatment (Ke et al., 2023)
This could be direct effects on the glycocalyx/endothelial function or potential anti-inflammatory effects. Heerspink noted most adults enrolled in the SURPASS trials had preserved kidney function, and additional studies enrolling adults with type 2 diabetes plus CKD with longer follow-up are needed
