Eli Lilly disclosed that its Phase 3 TRIUMPH‑4 study of retatrutide, a triple hormone receptor agonist targeting GIP, GLP‑1, and glucagon, produced a mean weight loss of 28.7 % at 68 weeks—roughly 71 pounds—for the highest dose cohort. The same cohort also achieved a 75.8 % reduction in knee pain as measured by the WOMAC score, the largest pain improvement reported for any obesity drug in a late‑stage trial.
The data confirm retatrutide’s dual benefit of weight loss and joint‑health improvement, positioning it as a potential next‑generation therapy that could surpass Lilly’s own Zepbound and Novo Nordisk’s Wegovy in efficacy. However, the drug remains investigational; regulatory approval and commercial launch are still pending. The trial also revealed a safety signal of dysesthesia—an abnormal sense of touch—reported in a subset of patients, and discontinuation rates were 18.2 % for the high dose versus 4 % for placebo, underscoring the need for careful dose optimization.
Lilly’s obesity franchise has been a key growth engine, with revenue from its incretin analogs rising from $9.35 billion in Q4 2023 to $15.56 billion in Q2 2025, a 38 % year‑over‑year increase. The company’s guidance for FY 2025 has been raised to $63–$63.5 billion, reflecting confidence in continued demand for its obesity portfolio and the potential upside from retatrutide. Management highlighted that the TRIUMPH‑4 results “demonstrate the powerful effect of retatrutide on body weight, pain, and physical function,” and that seven additional Phase 3 readouts are expected in 2026, which could broaden the drug’s therapeutic scope.
Market reaction to the announcement was positive: pre‑market trading showed a modest uptick, and Wells Fargo lifted its price target for Lilly from $1,100 to $1,200, citing the trial’s strong efficacy data and the company’s robust pipeline. The results are expected to reinforce investor confidence in Lilly’s obesity strategy and could influence future valuation multiples as the company moves closer to a potential approval.
The trial’s outcomes also highlight the competitive dynamics in the obesity market. While Zepbound and Wegovy are currently approved and generating revenue, retatrutide’s superior efficacy could shift market share if it secures FDA approval. The company’s focus on expanding the drug’s indications—such as obstructive sleep apnea and chronic low back pain—could further diversify its revenue streams and mitigate reliance on a single product.
Safety considerations remain a key factor for regulators and payers. The dysesthesia signal and higher discontinuation rates at the high dose suggest that dose‑titration strategies and patient selection will be critical in the eventual commercial rollout. Lilly’s ongoing investment in manufacturing capacity aims to support a potential launch, but the company must balance production scaling with the need to manage adverse events and maintain product quality.
In summary, the TRIUMPH‑4 topline results represent a significant milestone for Eli Lilly’s obesity pipeline, offering a compelling efficacy profile that could redefine the therapeutic landscape. The data, coupled with the company’s strong financial performance and forward guidance, underscore Lilly’s strategic positioning and the potential for future growth in the expanding obesity market.
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