On some level, calories in calories out has to be true. But these variables are not independent. Bodies respond to exercise by getting hungry and to calorie deficit by getting tired. Even absent that, bodies know how much food they want, and if you don’t give it to them they will tell you at increasing volume until you give in (not all bodies, of course, but quiet stomachs aren’t the target market for GLP-1s). A new breed of drugs, GLP-1 agonists, offer a way out of the latter trap by telling your body you’ve eaten, even when you haven’t, but leave many people fatigued. The newest GLP-1, retatrutide, may escape that trap too, with a mechanism so beautiful I almost don’t believe it.

How Jelly Beans Becomes Fat

Unfortunately in order to understand the beauty of retatrutide, you’re going to have to learn the basics of [...]

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Outline:

(00:56) How Jelly Beans Becomes Fat

(04:19) The Power Plant Managers

(08:21) How do GLP-1 Medications Work?

(11:04) The Side Effects

(13:32) Conclusion

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First published:
October 14th, 2025

Source:
https://www.lesswrong.com/posts/ahYpi49FNhxYBxanw/the-biochemical-beauty-of-retatrutide-how-glp-1s-actually

“The Biochemical Beauty of Retatrutide: How GLP-1s Actually Work” by Elizabeth

LessWrong (30+ Karma)