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One of the possible reasons for this is that metformin inhibits sodium-glucose cotransporter1 (SGLT1) on small intestinal epithelial cells, decreasing the intra- and extracellular Na + concentration gradient, thereby inhibiting intestinal glucose absorption and increasing glucose utilization (Lenzen et al., 1996

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stratifying by metabolic status, by genetic risk such as GBA and LRRK2 variants in Parkinsons or APOE in Alzheimers, by disease stage, and potentially by GLP-1R polymorphism is the most plausible route to a positive trial