ResearchSafe

Retatrutide Phase 3 data is out and the numbers are proper wild

Posted by peptidehead914 in Weight Loss & Metabolic - 6 points, 4 comments.

https://www.biopharmadive.com/news/lillys-retatrutide-tripleG-phase3-obesity-data/820851

So Lilly's triple-acting obesity drug retatrutide just hit its Phase 3 endpoint and the weight loss numbers are apparently bariatric-surgery level, which is basically the kind of result that makes you sit up and pay attention. It is a triple agonist hitting GLP-1, GIP, and glucagon receptors, so it is doing more than semaglutide or tirzepatide under the hood.

I am cautiously excited but also a bit annoyed at how these press releases always frame things. They never give you the actual percentage weight loss front and centre, you have to dig for it, and they conveniently skip over the side effect profile which for a triple agonist is going to be the real question mark. My own experience with GLP-1 compounds is that the appetite suppression is real but the fatigue and GI stuff can be rough, and adding glucagon receptor agonism on top of that is basically asking your liver and gut to do extra work they might not thank you for.

Anyone here been following the glucagon receptor angle specifically? I am curious whether the thermogenic effect from glucagon actually shows up meaningfully in real-world data or if it is just a nice mechanistic talking point.

Comments

  • medic738: Honestly the glucagon receptor thermogenic angle is what I find most interesting here. The mechanism makes sense on paper, glucagon increases energy expenditure through liver pathways, but whether that translates to meaningful real-world numbers is another thing. In my own tracking with GLP-1 compounds I saw maybe 8 to 10 percent weight loss over a few months but my resting metabolic rate did not move much, maybe 3 to 5 percent at best, and that could have been just from losing mass. Adding glu
  • peptidehead914: Ja that RMR barely shifting tracks with what I have seen in my own tracking too, basically the scale moves but the actual metabolic rate just kind of shrinks with the mass you lose which is frustrating. The glucagon thermogenic angle is the whole reason I am interested in retatrutide honestly, because if it actually bumps energy expenditure beyond what you would expect from weight loss alone that is a proper game changer, but I share your suspicion that the GI side effects are going to be the ce
  • fasted_scientist: Ngl I reckon you are spot on about the GI side effects. If the glucagon part is what drives the thermogenesis, the nausea might be too much to handle for most people. It is easy to see the metabolic bump on paper, but if you cannot keep food down, the math does not really matter.
  • peptidehead914: Ja exactly, the thermogenesis angle is lekker on paper but if you are doubled over the whole time it is pointless. I reckon the glucagon bit is going to be the make-or-break for tolerability, because the GLP-1 and GIP sides we already know about are not exactly gentle. Be interesting to see if they dose-titrate slower than tirzepatide to manage it, because that could be the difference between people actually staying on it versus dropping out by week four.

Community discussion - research and educational context only. Not medical advice.