Eli Lilly’s experimental injection retatrutide — a so‑called “triple‑G” drug that nudges three hunger hormones at once — produced what the company says are some of the largest weight losses yet reported in a late‑stage trial, while also easing knee pain in people with obesity and osteoarthritis.
What the trial showed
In the TRIUMPH‑4 readout, participants on the highest dose lost an average of 23.7% of body weight at 68 weeks when the analysis included everyone originally randomized, Lilly reported. Restricting the analysis to participants who stayed on treatment — effectively the best‑case scenario — the same dose produced an average weight loss of 28.7%.
Lilly also described striking improvements in knee osteoarthritis pain: measured reductions reached about 62.6% on a common pain scale, and more than one in eight trial participants reported being entirely free of knee pain by the end of the study.
The company emphasized that the trial population wasn’t limited to people whose main goal was weight loss; TRIUMPH‑4 tested the drug specifically in patients with obesity and knee osteoarthritis. Lilly said it expects to report results from seven additional late‑stage studies of retatrutide by the end of 2026. For more on the company’s public updates, see the Lilly news page.
How retatrutide works — and why it matters
Retatrutide activates three hormone receptors: GLP‑1, GIP and glucagon. That triple action is thought to blunt appetite and increase satiety more robustly than drugs that target only one or two of those pathways. That’s why observers have nicknamed it the “triple‑G” candidate.
By comparison, Lilly’s current blockbuster injection Zepbound (tirzepatide) targets GLP‑1 and GIP, and Novo Nordisk’s Wegovy targets GLP‑1 alone. In recent late‑stage studies, higher doses of tirzepatide produced around 22–23% weight loss, so retatrutide’s numbers — if replicated across other trials — would mark a meaningful step up in efficacy.
Analysts and investors have been watching closely: the obesity and diabetes drug market has ballooned into a multibillion‑dollar opportunity, and companies are racing to develop next‑generation treatments that drive faster, deeper or more durable weight loss.
Safety, tolerability and trial churn
The headline numbers came with caveats. Roughly 18% of participants on the highest retatrutide dose discontinued treatment because of side effects, versus about 4% in the placebo group. Lilly said many dropouts were linked to baseline body‑mass index and included some people who stopped because they felt they’d lost too much weight.
Common adverse effects mirrored those seen with other incretin‑class drugs: nausea affected about 43% of people on the top dose, diarrhea about 33%, and vomiting roughly 21%. More than 1 in 5 participants reported dysesthesia — unpleasant nerve sensations — though the company said these events were generally mild and seldom the reason for stopping the drug.
Those tolerability signals will matter for regulators and payers: high efficacy can be undercut by safety or adherence issues in the real world.
The competitive landscape and what comes next
Lilly is positioning retatrutide as a potential follow‑on to Zepbound and part of a broader obesity portfolio that also includes an investigational pill. Rival Novo Nordisk is pursuing its own multi‑agonist candidates and recently acquired rights to a China‑developed “triple” drug that could become a competitor further down the line.
Lilly says retatrutide has cleared its first late‑stage hurdle; the company expects further phase‑3 readouts next year. Approval timelines remain uncertain and will depend on results from the other trials, regulatory review, and how safety and tolerability balance against the drug’s strong efficacy signals.
A pragmatic note
These results are notable — both for the magnitude of weight loss and for the joint‑pain benefits — but they are an early chapter, not the last word. Cross‑trial comparisons are imperfect, and the experience of a tightly controlled clinical trial can differ from what patients face in routine care. Still, if retatrutide’s efficacy and safety profile hold up across the wider program, it could reshape options for people with severe obesity and obesity‑related complications.