Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression | npj Metabolic Health and Disease.
We report that in pre-clinical models with significant retatrutide (RETA, LY3437943)-induced weight loss, pancreatic cancer engraftment was reduced, tumor onset was delayed, and progression was attenuated resulting in a 14-fold reduction in tumor volume compared to only 4-fold reduction in single agonist semaglutide-treated mice. Despite weight re-gain after RETA withdrawal, the anti-tumor benefits of RETA persisted. Remarkably, RETA-induced protection extends to a lung cancer model with 50% reduced tumor engraftment, significantly delayed tumor onset, and mitigated tumor progression, with a 17-fold reduction in tumor volume compared to controls.
Studies were conducted on mice. They compared mice treated with sema vs retatrutide, and found that retatrutide was much more effective at reducing tumor size and delaying tumor growth. Effects on tumors lasted even after stopping retatrutide treatment, although weight did rebound back.
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Supra levels of Glucagon seem to be the key to reducing tumor size. Several studies have been looking at glucagon to treat some types of cancer. Here is one
https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202307271
In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo-vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR-dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response.
They found that glucagon by itself did not reduce or tumor size, but it acted more as an amplifier/facilitator for chemotherapy medicine. The combination of chemo + glucagon was more effective that chemo alone or glucagon alone.
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