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Although the actual mechanisms of MTX-induced liver and kidney damage are unknown, one of the hypotheses is the breakdown in cellular antioxidant defences, which increases the production of reactive oxygen species and nitrogen species, inhibits cytosolic NADP-dependent dehydrogenase and NADP malic enzyme, lowers glutathione (GSH), superoxide dismutase (SOD) and catalase levels and reduces the effectiveness of the antioxidant defence system protecting the cell against reactive oxygen species (Reference Savran, Cicek and Doguc7)

Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in sustain China: A 30-week, double-blind, phase 3a, randomized trial

Of note, there was a complex set of analyses to determine if the degree to which individuals adhered to their medication affect results

Straub et al., 2014b)

What effects do incretins have throughout the body