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Besides the well-known targets such as the inhibition of the mTOR signaling pathway, several additional metformin and phenformin targets (e.g., mGPDH, ATF3, STAT3, GSK3, cyclins) have been identified in other cancers (Thakur et al., 2019)
The theoretical benefit compared to the peptides is reduced receptor desensitisation and a different tolerability profile, though whether that translates to clinically meaningful differences in nausea, vomiting and discontinuation rates is still under investigation
The primary concern, rapid drops in blood sugar from GLP-1 therapy can temporarily worsen existing DR, which is why it has been highlighted in research
Fujieda, N., Umakoshi, K., Ochi, Y., Nishikawa, Y., Yanagisawa, S., Kubo, M., Kurisu, G
However, researchers noting the hypothalamic overlap where both metabolic hormones and melanocortin receptors converge may find interesting crosstalk dynamics worth investigating in preclinical models
The effects of early life stress, postnatal diet modulation, and long-term western-style diet on later-life metabolic and cognitive outcomes
