Eli Lilly and Company (LLY) released Phase 3 topline results Thursday showing that retatrutide, its next-generation weight loss candidate, achieved remarkable outcomes across multiple health markers. The TRIUMPH-4 trial evaluated the two highest investigational doses in adults with obesity or overweight and knee osteoarthritis who don't have diabetes.
Retatrutide is what's called a triple hormone receptor agonist, targeting GIP, GLP-1, and glucagon receptors simultaneously. Think of it as the pharmaceutical equivalent of attacking a problem from three angles instead of one. The approach appears to be paying off.
The Weight Loss Numbers
Both doses tested (9 mg and 12 mg) met all primary and key secondary endpoints at the 68-week mark. For weight loss specifically, retatrutide delivered an average reduction of up to 28.7% using both efficacy and treatment-regimen estimands. That's substantial by any measure.
But here's where it gets interesting: the drug wasn't just about shedding pounds. Participants experienced an average pain reduction of up to 4.5 points, representing a 75.8% decrease in knee pain. These dual benefits matter because obesity and osteoarthritis often travel together, creating a cycle where joint pain limits activity, which can worsen weight issues.
Bonus Benefits For Heart Health
Beyond the primary endpoints, retatrutide showed improvements in cardiovascular risk markers. At the highest dose, systolic blood pressure dropped by 14.0 mmHg. That's not trivial when you're talking about reducing heart disease risk in a population already facing elevated cardiovascular concerns.
Perhaps most striking: a post-hoc analysis revealed that 14.1% of patients on the 9 mg dose and 12.0% on the 12 mg dose were completely free of knee pain at 68 weeks. Compare that to just 4.2% on placebo. Some participants essentially went from chronic pain to no pain at all.
The Safety Profile
The most common adverse events matched what you'd expect from this drug class: nausea, diarrhea, constipation, vomiting, and decreased appetite. These are consistent with other incretin-based therapies currently on the market.
Discontinuation rates due to adverse events came in at 12.2% for the 9 mg dose and 18.2% for the 12 mg dose, compared to 4.0% for placebo. Those numbers suggest tolerability challenges at higher doses, though many patients clearly stuck with it.
What's Next
Additional results from the broader TRIUMPH program are expected in 2026. Those will include data on a 4 mg maintenance dose alongside the 9 mg and 12 mg doses evaluated in this trial.
Meanwhile, Lilly announced Wednesday it's investing over $6 billion in a new Huntsville, Alabama manufacturing facility. The site will produce orforglipron, the company's first oral GLP-1 receptor agonist in pill form. Lilly expects to submit orforglipron to global regulatory agencies for obesity approval by year-end.
LLY Price Action: Eli Lilly shares were up 1.50% at $1,008.56 at the time of publication on Wednesday.