Retatrutide Phase 3 Update: What We Actually Know So Far From the TRIUMPH-4 Trial

Alright, bros, let’s talk retatrutide.

We finally have some Phase 3 topline data from the TRIUMPH-4 study. Not the whole research. Not the peer-reviewed version. Just the high-level results Lilly chose to release. But even from that, there’s plenty to break down, clean up, and fact-check. So let’s dive in.

What Retatrutide Is and Why Anybody Cares

Retatrutide is Lilly’s experimental triple-agonist drug. It hits three metabolic pathways instead of one or two. GLP-1 handles appetite and slows gastric emptying. GIP enhances insulin secretion and may improve tolerability. The glucagon receptor activation appears to be the wild card that boosts energy expenditure and fat metabolism.

It’s still in Phase 3 trials and close to FDA approval. Based on the results we’re seeing, this thing has the potential to be a monster in the metabolic space.

What the TRIUMPH-4 Study Looked At

TRIUMPH-4 focused on two things:

1. Weight loss

2. Knee osteoarthritis symptoms

The people in the trial had obesity or overweight plus knee OA. Retatrutide was tested in two dosing groups:

9 mg weekly12 mg weeklyPlacebo

Treatments ran for 68 weeks.

The drug was escalated slowly, just like other GLP-1/GIP-based treatments, but the exact escalation schedule for Phase 3 has not been released.

So yes, we can infer from Phase 2 that they ramped up from a low dose (those studies started around 2 mg), but we cannot say that Phase 3 did the same.

The Weight Loss Numbers Are Just Absurd

Here’s the part everyone cares about.

On the full 12 mg dose, people who finished the study lost 28.7 percent of their body weight. That worked out to around 71 pounds on average. That’s basically bariatric surgery-level weight loss or better from a drug, and no, that’s not an exaggeration.

If you include everyone who started the study, even those who bailed out early, the average weight loss still comes in around 23.7 percent. Analysts peg the placebo-adjusted numbers at roughly 26.6 percent.

And to correct the record: baseline weights were around 248–250 pounds, not 300-plus. Doesn’t make the results any less wild. If anything, it makes the percent loss even more impressive.

Rumors were going around that Phase 3 weight loss was “underwhelming.” Yeah, not according to these data.

Knee Pain: The Second Big Result

This study wasn’t just about getting lean. It was about what happens when you reduce weight and improve metabolic markers in people with knee osteoarthritis.

Here’s what retatrutide did:

Knee pain was reduced 75–76 percent from baseline. About a 4.5-point drop on standard OA pain scales12–14 percent of participants became completely pain-free. Placebo? About 4 percent

Those are very real changes.

And to make sure we’re straight on this: TRIUMPH-4 did not compare retatrutide to gastric bypass. No direct comparison exists. Weight loss alone can improve knee pain, yes, but these reductions are bigger than we’d expect just from losing weight. There’s probably some metabolic/inflammatory angle at play.

Side Effects: The Usual Ones and a New One

Like all drugs in this class, retatrutide brought the standard GI side effects:

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Slowed gastric emptying.

Nothing surprising there. Most GLP-1 users know the drill.

But TRIUMPH-4 revealed something new:

Dysesthesia.

Dysesthesia = weird skin sensations. Burning. Tingling. Pins and needles. Static electricity vibes. Almost like a niacin flush.

Here’s what the data show:

12 mg: 20.9 percent9 mg: 8.8 percentPlacebo: 0.7 percent

It’s real. It’s dose-dependent. And no, there’s no evidence of nerve damage or anything dangerous. It’s mostly annoying, but it was significant enough to contribute to some dropouts.

There’s also prior evidence that retatrutide increases resting heart rate slightly more than other GLP-1 drugs, but Phase 3 heart rate data have not been released yet, so we can’t say much more.

Dropout Rates

Dropout rates were higher than what we’ve seen in trials for other obesity drugs:

18.2 percent on 12 mg12.2 percent on 9 mg4 percent on placebo

Primary reasons reported in topline releases:

Side effects: Excessive weight loss

We’ll know more once the complete data set drops.

What We Don’t Know Yet

Let’s clear this up, because this is where the internet gets ahead of itself.

We do not have:

Complete study ClinicalTrials.gov posted data, peer-reviewed publication, Detailed side effect tables, Heart rate data, Long-term tolerability information, Results from the other TRIUMPH studies, FDA submission.

The complete picture won’t show up until 2025 or 2026. If everything looks good across the entire program, approval would likely be in 2026 or 2027.

Final Thoughts

Based on what we have right now, retatrutide looks like the most powerful obesity-treatment drug ever tested. The weight loss is next-level. The osteoarthritis improvements are significant. And the side-effect profile, while real, is manageable — with dysesthesia being the only big unexpected twist.

But remember: this is just one Phase 3 trial. There are more on the way, and until we see complete datasets, peer-reviewed publications, and regulatory analysis, nothing is final.

As more information rolls out, I’ll keep you bros posted. This is going to be one of the biggest stories in the metabolic world over the next couple of years, and we’re just getting started.

I will have a video up on YouTube by this Monday.