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Despite these promising findings, some preclinical models have also reported paradoxical pro-tumor effects or significant adverse outcomes, such as exacerbating metastasis and cachexia, under specific conditions, highlighting context-dependent responses [148, 149]

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Cotadutide (MEDI0382) is the most extensively developed dual GLP-1/glucagon receptor agonist, showing significant improvements in glucose control, BW (likely mediated by reduced energy intake rather than increased energy expenditure), hepatic fat, and albuminuria in a small RCT on patients with T2D and overweight or obesity 45,46

To avoid the decrease in the SAMe pool in tumor cells that would result from activation of the polyamine pathway, the rate limiting enzyme of the salvage pathway, MTAP, appears also upregulated and is necessary for cancer growth [218]