Retatrutide 71 lb average loss is wild, but those discontinuation numbers bother me
Posted by rachel_ketogen in Weight Loss & Metabolic - 1 points, 4 comments.
Drug Discovery Trends ran a piece on Lilly's Phase 3 retatrutide data, and the headline number is honestly kind of jaw dropping. Up to 71 lbs average weight loss at the high dose over 72 weeks, which is right up there with surgical territory.
But the part that actually caught my eye was buried lower. The highest retatrutide dose had almost three times the adverse event discontinuation rate of tirzepatide in SURMOUNT-1. So the people who dropped out because of side effects were way higher, and that rarely gets talked about in the hype cycle.
For me, that changes the math. A protocol you cant stay on isnt really a protocol, no matter how good the average looks on paper. Curious if anyone here has watched these numbers move over time and whether the GI stuff actually settles or if its a hard stop for most people.
Comments
- weekendnate: Yeah, the efficacy ceiling on this one is honestly hard to ignore, but you're right that the discontinuation rate is the part nobody wants to sit with. A protocol you can't stay on isn't a protocol, full stop. What I've been watching is whether the GI stuff actually titrates down over a longer ramp, or if the receptor agonism is just too aggressive at the top doses to settle. My own experience on similar agents was that the first 4 to 6 weeks were rough, then it calmed down, but I'd never push
- rachel_ketogen: Appreciate you bringing up the titration question because thats exactly where I land too. The first month on tirz was rough for me, nausea was real around dose 3, but it did calm down by week 5 or 6 and then it was fine. What worries me with retatrutide is the triple agonism, thats a lot more receptors getting hit at once. Im wondering if the GI stuff at the top dose actually titrates or if its just a different beast entirely. Did yours stay manageable or were you constantly white knuckling it?
- tiredmira: Yeah that titration question is basically what I'm tracking too. From what I've seen on other multi-agonists, the GI events tend to front-load pretty hard and then settle if you go slow enough. But 3x the discontinuation rate vs tirz still feels like a signal even with a better ramp. I'd want to see the slower titration arm data before getting excited 😅
- rachel_ketogen: Yeah exactly, front-loading is what im curious about too. If the slower ramp arm shows the GI stuff calms down but dropout still stays high then it's something about the molecule itself. Thats the arm i want to see published. Did you come across any subgroup breakdowns or is everyone just waiting on the same thing?
Community discussion - research and educational context only. Not medical advice.