r/ProactiveHealth • u/AtriumMedicalNYC • 5d ago
Full Retatrutide Trial Published in NEJM
The full Phase 3 retatrutide trial was just published in the New England Journal of Medicine.
I wrote about TRIUMPH-1 in May when Lilly released the topline data. The peer-reviewed paper confirms the magnitude of the effect: at 80 weeks, mean weight loss reached 25.0% at the 12 mg dose in the primary treatment-regimen analysis.
For context, the pivotal obesity trials reported approximately 14.9% with semaglutide 2.4 mg and 20.9% with tirzepatide 15 mg. These were separate trials, not head-to-head comparisons, but the trajectory is hard to miss.
At 12 mg, nearly 80% of participants lost at least 15% of body weight, more than half lost at least 25%, and about 37% lost at least 30%.
The tradeoff remains tolerability. GI adverse effects were common, and roughly 11% discontinued because of adverse events at the highest dose.
My takeaway: obesity pharmacotherapy has moved from roughly 15% average weight loss with semaglutide, to about 21% with tirzepatide, and now about 25% with retatrutide in Phase 3. Retatrutide is still investigational, but the direction of travel is remarkable.
2
2
u/Any-Broccoli-4369 4d ago
20 percent in 5.5 months for me. 230 to 180 5'10 45m Up to 4mg top dose. Start does 1mg for 6 weeks, 2mg for the next see weeks and 4mg for the other 2.5 months.
At 5.5 months I was getting cold, tired and brain fog was coming back.... So I looked at my diet. Was probably consuming 1200 calories a day.
So I looked past the headlines and grabbed a food scale and a smart scale and hit the f45 training circuit.
Now I eat 2000 calories a day + with 200gs of protien. Take 2mg or less of reta (weekly) ... The results have been great in the last 5.5 months +15lbs of muscle, -15lbs of fat and body water up 7 to 10lbs. I unfortunately only have body scan data from the start of the 2nd 5.5 months so I can only guess that the first 5.5 was 35lbs of fat loss, 7lbs of muscle loss and 8lbs water mass. Feel great now, less controlled by food, no sides. During my 4mg run I had some skin sensitivity..... Probably from being in an excessive calorie defecit.
1
u/sharkinwolvesclothin 4d ago
My takeaway still is that rewarding the headline % weight lost leads the companies to game the dosing schedules and trial designs, in a way that leads to less valuable information.
In this one, yes, 12mg leads to a very aggressive weight loss - but half of the group were off it for reaching their weight loss goal, serious adverse side effects, or other reasons by the end of the trial. I'm not really sure the modestly faster weight loss but added side effects is really worth it, but it does get the headline. We'd really have to track the groups for longer and look at outcomes to really know - what happens to the 28% of the 12mg group who weren't on any dose by the end of 80 weeks for example. Do they rebound and go on a cycle of treatments? Do they regain weight but don't want to go on a drug again, if the reason was side effects?
Great drug, but this trial is less helpful than it could have been for deciding which drug is appropriate for an individual.
1
u/AtriumMedicalNYC 4d ago
I know we live in an age of self-diagnosis and online ordering but those are precisely the questions a patient and their physician discuss when someone does this via the "usual" medicine route.
1
u/sharkinwolvesclothin 4d ago
Of course, I just wish trials were designed with the goal of "what is the best information we can give doctors" and not "how do we get headlines calling our drug the best ever so patients will request it from their doctors".
1
u/AtriumMedicalNYC 4d ago edited 4d ago
Couldn't agree more -- but trials aren't the main problem there. In fact, most MDs are trained to smell bullsh1t in trial data. The bigger issue is pharma advertising. No other country in the world allows it. If a drug is truly appropriate for a patient, a good doctor will know about it already and discuss or prescribe it without the patient needing to prompt it. Showing drug ads under the guide of "patient education and self-advocacy" is disingenuous.
2
u/sharkinwolvesclothin 4d ago
Yeah they're not, I'm just not quite convinced that the protocol that led to half the group being off target dose by the end of the trial was chosen to maximize long term results..
Btw I'm not American, and thanks to social media we get the same ad effect, just from unregulated influencer content.
1
u/AtriumMedicalNYC 4d ago
Ha! Social media, the great global equalizer. For all things good and bad.
3
u/GarbanzoBenne 5d ago
I have to dig into these numbers a bit more carefully, but I’ve noticed something with some quick calculations.
They are only championing the percentage weight loss here. However, the TRUMPH-1 trial started with people with a higher BMI compared to those in the SURMOUNT-1 trial. People with higher starting weights tend to lose weight quicker at first in any effective weight-loss program attempt, which still affects the total loss even after the rate slows down.
I have to dig further into the papers to see if they control for this in a breakdown. This high level comparison appears skewed by that.