Prepared by: Research Desk. Sources are linked for verification.

Status: Investigational. Retatrutide is not approved by the FDA. The FDA states that it has "not been found safe and effective for any condition" and that it cannot be used in compounding under federal law [1]. Our approval status page has the full regulatory picture.

TRIUMPH-4 is the phase 3 study of retatrutide in adults with overweight or obesity and knee osteoarthritis. This page covers four things:

• what the trial registered;

• what it measured;

• what Eli Lilly announced;

• what is still missing from the public record.

One caveat applies to everything below. As of 21 October 2026, the TRIUMPH-4 results in our verified sources are company-reported topline data from a press release. They are not a peer-reviewed journal publication [2]. Topline figures are a first summary from the sponsor. A full paper normally adds methods, statistical analyses, subgroup data and complete safety tables, and it goes through independent peer review.

TRIUMPH-4 at a glance

Why a knee osteoarthritis trial?

Most obesity drug trials use body weight as the main outcome. TRIUMPH-4 added a second co-primary endpoint tied to a specific condition: knee pain in people with osteoarthritis.

The knee is a weight-bearing joint. Researchers have therefore asked a specific question: when body weight falls substantially in a controlled trial, do joint-related symptoms also change in a measurable way?

In a co-primary design, both endpoints are pre-specified as main outcomes, and each is tested against placebo. Reading the trial properly means looking at both numbers, not only the weight figure that tends to dominate headlines. Our explainer on how to read a retatrutide trial covers co-primary endpoints, placebo comparison and weight-change reporting in more detail.

What WOMAC measures

WOMAC (the Western Ontario and McMaster Universities Osteoarthritis Index) is a questionnaire used in osteoarthritis research. Participants rate their pain, stiffness and physical function. TRIUMPH-4 used the pain subscale as a co-primary endpoint [2][3].

Three points matter when reading WOMAC results:

• It is self-reported. Scores reflect how participants rate their own symptoms. That is why blinding matters: participants who suspect which arm they are in could rate their symptoms differently.

• Placebo groups can change too. TRIUMPH-4's placebo arm recorded a reduction in pain score [2]. The relevant figure is the difference between arms, not the change within one arm.

• Scale versions differ. WOMAC can be scored on different numeric scales. A full publication should state which version was used, so that point changes can be compared with other studies.

Reported results by arm

Lilly's release reported week-68 results for the two retatrutide arms and the placebo arm [2]. In line with this site's approach, we describe the arms as lower-strength and higher-strength rather than listing amounts.

Source: Eli Lilly press release, 11 December 2025 [2]. Company-reported topline data; not peer-reviewed.

Several observations follow from the table alone:

• Weight change was larger than in phase 2. The figures exceed the average reductions recorded in the 48-week phase 2 obesity trial of retatrutide, which enrolled 338 adults [4]. The populations, durations and analysis methods differ, so the numbers are not directly comparable.

• Pain-score changes were similar between the two retatrutide arms. The two arms recorded near-identical pain-score reductions, even though their weight change differed by a little over two percentage points.

• The placebo arm also recorded a pain-score reduction. This is why the between-arm difference is the figure to focus on.

What the release leaves out matters just as much. It does not set out in full:

• the confidence intervals;

• the statistical estimand used;

• how missing data were handled;

• results for the other WOMAC subscales;

• any imaging or structural joint outcomes.

A peer-reviewed paper would be expected to include these details.

Adverse events and discontinuations

The release listed the most frequently reported adverse events: nausea, diarrhea, constipation, vomiting and decreased appetite [2]. A 2024 review of GLP-1 medicines describes gastrointestinal events of this kind across the drug class more broadly [5].

Two safety figures from TRIUMPH-4 drew particular attention:

Source: Eli Lilly press release, 11 December 2025 [2].

According to the release, the adverse-event discontinuation figures include participants who stopped because of perceived excessive weight loss [2]. Lilly also reported that overall rates of discontinuing the study drug were similar across groups [2].

The release does not give a full breakdown of reasons. From the topline data alone, it is not possible to tell how many discontinuations were linked to each type of event.

In TRIUMPH-4, dysesthesia was reported more often in the higher-strength arm than in the lower-strength arm, and rarely with placebo [2]. A full publication should clarify how severe it was, when it began and how long it lasted. Our page on retatrutide side effects collects the adverse events listed across the published trial reports.

How TRIUMPH-4 fits the wider TRIUMPH program

TRIUMPH-4 is one of several registered phase 3 studies. The others include:

• TRIUMPH-1 [6];

• TRIUMPH-2, in adults with obesity and type 2 diabetes, since published in The Lancet [9];

• TRIUMPH-3 [7];

• TRIUMPH-5 [8].

A separate phase 3 trial, TRANSCEND-T2D-1, studied retatrutide in adults with type 2 diabetes [10]. Each trial enrolls a different population, so results from one cannot be carried over directly to another.

A May 2026 industry pipeline summary listed an FDA decision for retatrutide as a 2027 event [11]. That is a projection, not a regulatory commitment. Retatrutide remains investigational, and the FDA has issued warnings to companies marketing it outside trials [1].

For the trial-by-trial overview, see our retatrutide guide. To follow registry changes such as status updates and posted results, see how to track the TRIUMPH trials on ClinicalTrials.gov.

What to watch for next

• Peer-reviewed publication. Lilly said detailed results would be presented at a medical meeting and published in a journal [2]. Our verified sources do not show a full paper as of this update.

• Registry results posting. The ClinicalTrials.gov record may eventually carry a results section with participant flow and adverse-event tables [3].

• Secondary endpoints. These include stiffness, physical function and any joint-structure measures.

• Safety detail. This means the severity and course of dysesthesia, plus a reason-by-reason account of discontinuations.

We update this page when any of these appear. Our About page explains how sources are selected and how updates are logged.

Further reading

A good book can make dense study reports much easier to follow. These criteria are worth weighing when comparing titles:

• Author background. Look for authors with direct research experience.

• Sourcing. Endnotes that point to primary studies are a strong sign of quality.

• Recency. A recent publication date matters in fast-moving fields.

• Methods coverage. The best titles explain randomization, blinding, endpoints and placebo responses clearly.

Format and price matter too. Print editions work well as a desk reference, while ebooks and audiobooks often cost less, so compare list prices across editions. Our curated list of books about clinical trials applies these criteria.

Titles that explain statistics in plain language tend to stay useful longest, because the same concepts come up in every new study report.

Frequently asked questions

Is retatrutide approved for knee osteoarthritis?

No. Retatrutide is investigational and is not approved for any condition. The FDA states that it has not been found safe and effective for any condition [1].

Were the TRIUMPH-4 results peer-reviewed?

Not in the sources available to us as of 21 October 2026. The figures come from Lilly's 11 December 2025 press release. That release said full results would follow at a medical meeting and in a journal [2].

What were the TRIUMPH-4 co-primary endpoints?

The two co-primary endpoints were change in body weight and change in WOMAC pain score, both measured at week 68 [2][3]. According to the release, both retatrutide arms recorded larger changes than placebo on each measure.

Why did some participants discontinue the study drug?

The release reported adverse-event discontinuation rates of 12.2% and 18.2% in the two retatrutide arms, against 4.0% with placebo. These figures include discontinuations attributed to perceived excessive weight loss [2]. A full reason-by-reason breakdown has not yet been published.

Related on this site

• Retatrutide, trial by trial

• Retatrutide: mechanism, trial findings and side effects explained

• Is retatrutide FDA approved? Legal status and approval timeline

• Retatrutide side effects: what the trial reports list

• How to read a retatrutide trial: endpoints, placebo and weight change

• Retatrutide vs tirzepatide: how the trial designs and data compare

Last updated: 21 October 2026.

Not medical advice. This page reports published research and regulatory records for information only.

Research-only notice: Content on this site is provided for research and educational purposes only and is not intended for human use. It is not medical advice.

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