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photochemsyn 5 days ago

The developers of these new peptide-based hormone-acting drugs like semaglutide(ozempic) could be called biohackers, but the system they're hacking on - the human endocrine system - is a delicate system. Introducing semi-synthetic mimics of native hormones can go wrong in all kinds of ways, and hormone-analogue drugs have a poor track record (anabolic steroids, DES, etc.) so extra caution makes sense.

Semaglutide is based on a 31-amino acid polypeptide that mimics the human GLP-1 hormone. At position 26, the lysine side chain is conjugated with a fatty diacid chain, to slow degradation and prolongs half-life, and there are some other modifications. However, the target - the GLP receptor - is not just expressed in the intestinal tract but all through the body, in muscle, central nervous system, immune system, kidneys and others. So some unexpected effects beyond the desired ones are likely.

Semaglutide was recently shown to have potent effects on the heart, and possibly beneficial to certain heart disease conditions associated with obesity. Makes me suspect this drug should be restricted to clinically obese cases where strong intervention with close medical supervision is needed. However for healthy people who just want to lose a relatively small amount of weight it really doesn't seem wise.

"Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization..." (June 2024)

https://www.nature.com/articles/s41467-024-48970-2