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In preclinical models, comparison of cotadutide, a glucagon/GLP-1 dual RA, and liraglutide demonstrated superior reduction of hepatic de novo lipogenesis and enhancement of hepatocyte mitochondrial oxidative capacity (similar to levels stimulated by glucagon mono-agonismsuggesting restoration of mitochondrial function is a glucagon-specific benefit) [39]

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Efficacy studies have demonstrated this additive effect with metformin, sulfonylureas, and thiazolidinediones given in combination with saxagliptin and linagliptin

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Sadhu A, Upadhyay P, Agrawal A, Ilango K, Karmakar D, Singh GPI, et al