Retatrutide's clinical trials show 38% of weight loss is muscle, but bodybuilders report fat loss with muscle kept. The hypothesis: retatrutide raises FGF-21, which burns fat while sparing muscle in lean people, but obese people are resistant to FGF-21. That gap could explain why the drug works differently in real life than in trials.
There's this hot peptide, retatrutide, GLP-3.
Retatrutide. Retatrutide. Retatrutide. This is going to be a trillion-dollar drug.
Maybe you've heard the buzz, and the rumor in the bodybuilding and biohacking communities is that it causes fat loss without causing muscle loss. Now here's the thing where I've been hung up. That is not what the clinical trials show. In people with obesity, roughly 38% of weight loss is lean mass loss. So why are the anecdotes from bodybuilders and biohackers so different? What's actually going on? And at first glance, you might be thinking what I thought first: differences in protein intake, creatine, and probably unreported anabolics. And sure, that's part of it. But I think there's actually something deeper happening that no one is talking about. Retatrutide is different than semaglutide, GLP-1, or tirzepatide for one key reason: it has a glucagon receptor agonist component. And that matters because the the hormone glucagon can increase another hormone called FGF-21 made by the liver. Now, why do we care about this? Why do we care about FGF-21? Because in human studies, FGF-21 can increase energy expenditure, increase fat burning, fat cell uncoupling, and thermogenesis. And importantly, FGF-21 is muscle sparing. But here is the catch. Here is the linchpin. Here's the key. Obesity is an FGF-21 resistant state. Let that sink in. Let's put this all together. If retatrutide does increase FGF21, and lean individuals are more sensitive to the FGF21 hormone, and obesity is an FGF21-resistant state, that means we could have a scenario where lean metabolically healthy people are biased towards losing more fat, burning more calories, and preserving more muscle tissue on retatrutide, GLP-3, than what we see in the published literature. That could explain the disconnect between what people are reporting anecdotally and what's been published. Now, this isn't proven without a shadow of a doubt, but mechanistically it's very plausible. I'm curious to hear what you think. And if you want a deep dive breakdown into all the different GLPs and their evolution, check the link below.
