Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial

Rhea-AI Summary

Eli Lilly (NYSE: LLY) announced positive topline Phase 3 TRIUMPH-4 results for investigational triple agonist retatrutide in adults with obesity and knee osteoarthritis at 68 weeks. At the highest dose (12 mg) retatrutide lowered body weight by up to 28.7% (71.2 lbs) and reduced WOMAC pain by up to 4.5 points (75.8%). The trial tested 9 mg and 12 mg doses; 84.0% of participants had baseline BMI ≥35 kg/m². Secondary findings included substantial proportions achieving ≥25% weight loss (58.6% at 12 mg), a systolic blood pressure reduction of 14.0 mmHg at the highest dose, and improvements in non-HDL cholesterol, triglycerides, and hsCRP.

Common adverse events were gastrointestinal (nausea up to 43.2%) and dysesthesia (up to 20.9%); discontinuations for adverse events were 12.2% (9 mg) and 18.2% (12 mg). Seven additional Phase 3 readouts are expected in 2026.

Positive

• Weight loss up to 28.7% (71.2 lbs) at 12 mg, 68 weeks
• WOMAC pain reduction up to 4.5 points (75.8%)
• 58.6% of patients achieved ≥25% weight loss at 12 mg
• Systolic blood pressure lowered by 14.0 mmHg at highest dose

Negative

• Discontinuations for adverse events 18.2% at 12 mg
• Nausea occurred in up to 43.2% of patients (12 mg)
• Dysesthesia reported in 20.9% of patients (12 mg)

Key Figures

Weight loss (efficacy estimand) 28.7% (71.2 lbs) Retatrutide 12 mg at 68 weeks in TRIUMPH-4

WOMAC pain reduction 4.5 points (75.8%) Max reduction on WOMAC pain subscale vs 6.0-point baseline

Baseline BMI ≥35 84.0% Participants in TRIUMPH-4 with BMI ≥35 kg/m² at baseline

≥25% weight loss 58.6% Retatrutide 12 mg group achieving ≥25% loss (efficacy estimand)

Free of knee pain 12.0% vs 4.2% Retatrutide 12 mg vs placebo at 68 weeks (post-hoc)

SBP reduction 14.0 mmHg Systolic blood pressure drop at highest retatrutide dose

Nausea incidence 43.2% vs 10.7% Retatrutide 12 mg vs placebo gastrointestinal adverse event

Dysesthesia incidence 20.9% vs 0.7% Retatrutide 12 mg vs placebo sensory adverse event

Market Reality Check

$993.64 Last Close

Volume Volume 2,930,969 vs 20-day avg 3,630,281 (relative volume 0.81x) ahead of the trial update. normal

Technical Price at $993.64 trades above 200-day MA $813.52 and sits 10.64% below the $1,111.99 52-week high.

Peers on Argus

LLY’s pre-news gain of 1.16% came alongside smaller moves in large-cap peers: NVO +3.48%, JNJ +2.97%, and modest changes in ABBV, AZN, NVS, with no peers flagged in the momentum scanner.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 09	Capex expansion	Positive	-1.5%	Announced ><b>$6B</b> Alabama API facility to support orforglipron and other drugs.
Dec 09	Acquisition close	Positive	-1.5%	Completed tender offer and acquisition of Adverum with cash and CVR structure.
Dec 09	Oncology Phase 3	Positive	-1.5%	Jaypirca Phase 3 data showed <b>80%</b> reduction in progression or death vs BR.
Dec 08	Dividend declaration	Positive	-1.3%	Declared <b>$1.73</b> first‑quarter 2026 dividend with March <b>10</b> payment date.
Dec 08	Board change	Positive	-1.3%	Re‑elected Nobel laureate Carolyn Bertozzi to board and key committees.

Pattern Detected

Recent positive strategic, clinical, and capital-investment news has often been followed by modest single-day share-price declines, suggesting a pattern of profit-taking on good news.

Recent Company History

Over the past two months, Lilly reported several major developments, including positive Phase 3 data for Jaypirca in CLL/SLL, strong Phase 2 weight-loss data for eloralintide, and successful Phase 3 trials for oral GLP‑1 orforglipron, alongside a new $6 billion API facility announced on Dec 9, 2025 and a $1.73 quarterly dividend declaration. Despite broadly positive news flow, the stock often traded down slightly in the following session, underscoring a tendency toward profit‑taking after good news.

Market Pulse Summary

This announcement details successful Phase 3 TRIUMPH‑4 results for retatrutide, with up to 28.7% (71.2 lbs) weight loss and marked reductions in knee osteoarthritis pain and improved function. Seven additional Phase 3 readouts are expected in 2026, adding to an already active clinical pipeline. Investors may monitor forthcoming full data presentations, durability of efficacy, adverse-event profiles such as GI symptoms and dysesthesia, and how this obesity asset complements Lilly’s broader incretin and weight‑management portfolio.

Key Terms

glp-1 medical

"a first-in-class GIP, GLP-1 and glucagon triple hormone receptor agonist"

GLP-1 (glucagon-like peptide-1) is a natural hormone in the body that helps regulate blood sugar levels and appetite. Its significance to investors lies in its role as the basis for a class of medications that address conditions like type 2 diabetes and obesity, which are large and growing markets. Advances or investments in GLP-1-based treatments can signal opportunities in healthcare innovation and potentially impact pharmaceutical companies’ growth.

phase 3 medical

"first successful Phase 3 trial evaluating the safety and efficacy"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

AI-generated analysis. Not financial advice.

In TRIUMPH-4, participants with obesity and knee osteoarthritis taking retatrutide 12 mg lost an average of 28.7% of their body weight at 68 weeks

Retatrutide reduced WOMAC pain scores by up to an average of 4.5 points (75.8%) and significantly improved measures of physical function, with more than 1 out of 8 retatrutide-treated patients completely free from knee pain at the end of the trial 

Seven additional Phase 3 trials evaluating the investigational once-weekly treatment in obesity and type 2 diabetes are expected to complete in 2026

INDIANAPOLIS, Dec. 11, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the Phase 3 TRIUMPH-4 clinical trial evaluating the safety and efficacy of the two highest investigational doses of retatrutide, a first-in-class GIP, GLP-1 and glucagon triple hormone receptor agonist, in adults with obesity or overweight and knee osteoarthritis, and without diabetes, as an adjunct to healthy diet and physical activity. In this global registration trial, where 84.0% of participants had a baseline BMI of ≥35 kg/m², each dose of retatrutide (9 mg and 12 mg) met all primary and key secondary endpoints, delivering significant weight loss and improvements in pain and physical function at 68 weeks using both the efficacy and treatment-regimen estimands.^1,2 For the co-primary endpoints, retatrutide lowered weight by up to an average of 28.7% (71.2 lbs) and reduced pain by up to an average of 4.5 points (75.8%) using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.³

"People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. "We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function. With seven additional Phase 3 readouts expected in 2026, we believe retatrutide could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis."

TRIUMPH-4 Efficacy Estimand Results 

	Retatrutide 9 mg	Retatrutide 12 mg	Placebo
Co-Primary Endpoints
Percent change in body weight from avg. baseline of 112.7 kg (248.5 lbs; 40.4 kg/m² BMI)	-26.4%   (-29.1 kg; -64.2 lbs)	-28.7%   (-32.3 kg; -71.2 lbs)	-2.1%   (-2.1 kg; -4.6 lbs)
Change in WOMAC pain subscale score from avg. baseline of 6.0 points	-4.5 points (-75.8%)i	-4.4 points (-74.3%)i	-2.4 points (-40.3%)i
Secondary Endpoints
Acheived ≥25% weight loss	47.7 %	58.6 %	1.3 %
Acheived ≥30% weight lossii	30.5 %	39.4 %	0.8 %
Acheived ≥35% weight lossii	18.2 %	23.7 %	0.0 %
Change in WOMAC physical function subscale score from avg. baseline of 5.8 points	-4.1 points (-71.8%)i	-4.2 points (-73.7%)i	-2.1 points (-35.6%)i
Acheived ≥70% reduction in WOMAC pain subscaleii	73.0 %	67.7 %	26.2 %

iPercent change in the WOMAC pain subscale score and percent change in the WOMAC physical function subscale score were not pre-specified and were estimated from a post-hoc analysis. iiNot controlled for multiplicity.

In additional secondary endpoints, retatrutide reduced known markers of cardiovascular risk, including non-HDL cholesterol, triglycerides, and high-sensitivity C-reactive protein (hsCRP), and at the highest dose lowered systolic blood pressure by 14.0 mmHg, using the efficacy estimand.⁴ In an additional post-hoc analysis, 14.1% of patients on retatrutide 9 mg and 12.0% patients on retatrutide 12 mg were completely free of knee pain at 68 weeks compared to 4.2% on placebo, based on the observed efficacy estimand data.

For the treatment-regimen estimand, each dose level of retatrutide led to statistically significant improvements in both co-primary and all secondary endpoints. The treatment-regimen estimand results for the co-primary endpoints were:

• Percent change in body weight: -20.0% (-22.9 kg; -50.5 lbs; 9 mg); -23.7% (-27.2 kg; -60.0 lbs; 12 mg) and -4.6% (-5.3 kg; -11.7 lbs; placebo)
• Change in WOMAC pain subscale score: -4.0 points (-67.2%; 9 mg), -3.7 points (-62.6%; 12 mg) and -2.1 points (-35.1%; placebo)⁵

Consistent with the types of adverse events seen in clinical trials for other incretins, the most common adverse events among participants treated with retatrutide (9 mg and 12 mg, respectively) were nausea (38.1% and 43.2%) vs. 10.7% with placebo, diarrhea (34.7% and 33.1%) vs. 13.4% with placebo, constipation (21.8% and 25.0%) vs. 8.7% with placebo, vomiting (20.4% and 20.9%) vs. 0.0% with placebo, and decreased appetite (19.0% and 18.2%) vs. 9.4% with placebo. Dysesthesia occurred in 8.8% and 20.9% (9 mg and 12 mg, respectively) of patients treated with retatrutide, compared to 0.7% with placebo. These dysesthesia events were generally mild and rarely led to treatment discontinuation. Overall treatment discontinuation rates were similar across the retatrutide and placebo treatment arms. Discontinuation rates due to adverse events were 12.2% and 18.2% with retatrutide 9 mg and 12 mg, respectively, compared to 4.0% with placebo. These rates were highly correlated with baseline BMI and included discontinuations for perceived excessive weight loss. For patients with a baseline BMI ≥35, discontinuation rates due to adverse events were 8.8% and 12.1% for the 9 mg and 12 mg doses, respectively, compared to 4.8% with placebo.

Detailed TRIUMPH-4 results will be presented at a future medical meeting and published in a peer-reviewed journal. Additional results from the TRIUMPH program, which include a maintenance dose of 4 mg in addition to the 9 mg and 12 mg doses tested in this trial, are expected in 2026.

About retatrutide
Retatrutide is an investigational once-weekly triple hormone receptor agonist. Retatrutide is a single molecule that activates the body's receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Lilly is studying retatrutide in several Phase 3 clinical trials to evaluate its potential efficacy and safety in obesity and overweight with at least one weight-related medical problem, type 2 diabetes, knee osteoarthritis, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease.

About TRIUMPH-4 and the TRIUMPH clinical trial program
TRIUMPH-4 (NCT05869903) is a Phase 3, 68-week, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of retatrutide with placebo in adults with obesity or overweight and knee osteoarthritis. The study randomized 445 participants in a 1:1:1 ratio to receive either retatrutide 9 mg or 12 mg, or placebo. The objective of the study was to demonstrate that retatrutide is superior to placebo in WOMAC pain subscale score reduction and in body weight reduction from baseline to week 68 in people with a BMI ≥27.0 kg/m² and who met American College of Rheumatology Criteria (clinical and radiological) for knee osteoarthritis. Participants randomized to retatrutide initiated treatment with 2 mg once weekly and increased the dose in a step-wise approach every four weeks until reaching the target dose of 9 mg (via steps at 2 mg, 4 mg and 6 mg) or 12 mg (via steps at 2 mg, 4 mg, 6 mg and 9 mg).

The initial TRIUMPH Phase 3 global registrational clinical development program is evaluating the safety and efficacy of retatrutide for the treatment of obesity and overweight, obstructive sleep apnea and knee osteoarthritis in people with obesity and overweight across four global registrational trials. The program, which began in 2023, has enrolled more than 5,800 participants and additional results are anticipated next year. The TRIUMPH clinical trial program includes five doses of retatrutide: 2 mg, 4 mg, 6 mg, 9 mg and 12 mg. Across all studies, participants randomized to retatrutide initiated treatment with 2 mg once weekly and increased the dose every four weeks until reaching their target dose. The target doses in TRIUMPH-1 and TRIUMPH-2 are 4 mg, 9 mg and 12 mg, while target doses in TRIUMPH-3 and TRIUMPH-4 are 9 mg and 12 mg.

Endnotes and References 

1. The efficacy estimand with weight management represents efficacy in all randomized participants who remained on the study intervention (with possible dose modifications) without initiating prohibited weight management treatments. The efficacy estimand with knee osteoarthritis pain represents efficacy in all randomized participants who remained on the study intervention (with possible dose modifications) without initiating prohibited weight management and/or pain treatments.
2. The treatment-regimen estimand with weight management represents the estimated average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments. The treatment-regimen estimand with knee osteoarthritis pain represents the estimated average treatment effect regardless of adherence to study intervention assuming no treatment benefit should participants need significant actions associated with lack of efficacy.
3. WOMAC is a patient-reported questionnaire validated in osteoarthritis for assessing pain, stiffness and physical function, with scores normalized to a 0–10 scale where higher values indicate worse symptoms.
4. Not controlled for multiplicity.
5. Percent change in the WOMAC pain and physical function subscale scores were not pre-specified and were estimated from a post-hoc analysis.

About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about retatrutide as a potential treatment for adults with obesity or overweight and knee osteoarthritis, potential efficacy and tolerability of retatrutide, and the timeline for future readouts, presentations, and other milestones relating to retatrutide and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with expectations or study results to date, that retatrutide will prove to be a safe and effective treatment for obesity or overweight and knee osteoarthritis or other potential indications, that retatrutide will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. 

Trademarks and Trade Names 
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Refer to:	Niki Biro; niki_biro@lilly.com; 317-358-9074 (Media)
	Michael Czapar; czapar_michael_c@lilly.com; 317-617-0983 (Investors)

 

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SOURCE Eli Lilly and Company

FAQ

What did Eli Lilly announce about retatrutide (LLY) on December 11, 2025?

Lilly reported positive Phase 3 TRIUMPH-4 topline results showing up to 28.7% weight loss and up to 4.5-point WOMAC pain reduction at 68 weeks.

How much weight did retatrutide (LLY) produce in TRIUMPH-4 at 68 weeks?

Retatrutide 12 mg reduced weight by an average of 28.7% (71.2 lbs) using the efficacy estimand at 68 weeks.

What pain improvements did retatrutide (LLY) show in TRIUMPH-4 for knee osteoarthritis?

Retatrutide lowered WOMAC pain scores by up to 4.5 points (75.8%) at 68 weeks versus baseline.

What were the main side effects and discontinuation rates for retatrutide (LLY) in TRIUMPH-4?

Common adverse events included nausea (up to 43.2%), diarrhea and vomiting; discontinuations for adverse events were 12.2% (9 mg) and 18.2% (12 mg).

What proportion of patients achieved large weight-loss thresholds with retatrutide (LLY) in TRIUMPH-4?

At 12 mg, 58.6% achieved ≥25% weight loss, 39.4% achieved ≥30%, and 23.7% achieved ≥35%.

When will additional Phase 3 retatrutide (LLY) results be available?

Lilly expects seven additional Phase 3 trial readouts from the retatrutide program to complete in 2026.