Retatrutide phase 3 trial shows 30% average weight loss at 104 weeks

Overview

Updated 4 days ago

Eli Lilly's obesity drug retatrutide met its goals in two late-stage trials published the same day. The 12 mg dose produced 30.3% average weight loss over 104 weeks in adults with obesity, a level once seen mainly after bariatric surgery. In 1,152 adults with type 2 diabetes, the same dose cut weight 18.8% at 80 weeks, and 79% reached an HbA1c of 6.5% or lower.

Retatrutide is a once-weekly injection that activates three hormone receptors: GIP, GLP-1, and glucagon, one more than Wegovy or Zepbound. The results, published in the New England Journal of Medicine and The Lancet, set up a regulatory filing. Lilly plans to submit a biologics license application to the FDA in the first quarter of 2027.

Why it matters

If approved, a once-weekly injection could deliver bariatric-surgery-level weight loss without surgery, reshaping how obesity is treated.

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Key Indicators

28.3%

Average weight loss at 80 weeks (12 mg)

Per Lilly's topline; the NEJM publication reports 25.0% for the same 12 mg endpoint. The 9 mg dose produced 25.9% and the 4 mg dose produced 19.0% per Lilly.

18.8%

Average weight loss in diabetes trial at 80 weeks (12 mg)

TRIUMPH-2 per The Lancet treatment-regimen estimand; Lilly's topline reported 20.8%. Placebo produced 5.1%.

79%

Share of 12 mg diabetes group reaching HbA1c of 6.5% or lower

At week 80 in TRIUMPH-2, vs 26.3% on placebo. The 4 mg dose reached 73.1% and the 9 mg dose reached 79.2%. About 6 in 10 also moved below the BMI cutoff for obesity.

23.4%

Weight loss at 80 weeks, 12 mg group with BMI of 35 or higher (diabetes trial)

In TRIUMPH-2, adults with a baseline BMI of 35 or higher lost an average of 23.4% (about 60.8 pounds) on the highest dose, per the peer-reviewed results.

Voices

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People Involved

Ania Jastreboff, M.D., Ph.D.

Lead investigator of TRIUMPH-1; Professor of Medicine & Pediatrics (Endocrinology), Yale School of Medicine

Directs the Yale Obesity Research Center (Y-Weight)

Organizations Involved

Eli Lilly and Company

Pharmaceutical company

Sponsor of TRIUMPH-1 and developer of retatrutide

Indianapolis-based drugmaker developing retatrutide, a GIP, GLP-1, and glucagon triple hormone receptor agonist.

Yale Obesity Research Center (Y-Weight)

Academic research center

Home institution of the trial's lead investigator

University research center that has led several landmark incretin drug trials, including TRIUMPH-1.

New England Journal of Medicine

Peer-reviewed medical journal

Publisher of the TRIUMPH-1 results

Peer-reviewed medical journal that published the TRIUMPH-1 phase 3 trial (article NEJMoa2604169).

Timeline

July 2023 September 2026

6 events Latest: September 29th, 2026 · 1 week ago

Tap a bar to jump to that date

September 2026
NEJM publishes TRIUMPH-1 results
Latest Publication

The New England Journal of Medicine publishes the Phase 3 trial, including 30.3% average weight loss at 104 weeks on the 12 mg dose.
September 29th, 2026
TRIUMPH-2 diabetes trial results published in The Lancet
Publication

The Lancet publishes the phase 3 trial of 1,152 adults with obesity and type 2 diabetes. The 12 mg dose produced 18.8% average weight loss at 80 weeks, and 72% of that group reached an HbA1c of 6.5% or lower.
September 29th, 2026
June 2026
ADA presents TRIUMPH-1 and TRANSCEND-T2D-1
Conference presentation

Full results presented at the ADA 86th Scientific Sessions show weight loss plus improvements in knee osteoarthritis pain and obstructive sleep apnea.
June 6th, 2026
May 2026
Lilly announces positive topline results
Corporate statement

All three retatrutide doses meet primary and key secondary endpoints; the 12 mg dose shows 28.3% average weight loss at 80 weeks.
May 21st, 2026
April 2026
TRIUMPH-1 completes main study
Trial completion

The 80-week master trial and its 104-week pre-specified extension finish, per ClinicalTrials.gov records.
April 30th, 2026
July 2023
TRIUMPH-1 trial opens
Trial launch

Eli Lilly begins a Phase 3, placebo-controlled trial of retatrutide in adults with obesity or overweight and at least one weight-related comorbidity.
July 10th, 2023

Scenarios

FDA Approves Retatrutide for Obesity

Likely Resolves by End of 2028

Discussed by: Lilly's topline release and analysts covering the obesity drug market

With two positive Phase 3 programs (TRIUMPH-1 and TRANSCEND-T2D-1), Lilly files a New Drug Application for retatrutide in chronic weight management. The FDA grants priority review and approves the drug, giving patients a once-weekly option that reaches roughly 30% average weight loss. Approval would position retatrutide as the most efficacious obesity injection on the market, above Zepbound and Wegovy.

Basket Trial Results Shape the Label

Likely Resolves by Q2 2027

Discussed by: Lilly's June 2026 ADA presentation of the TRIUMPH-1 and TRANSCEND-T2D-1 programs

The two nested basket trials — knee osteoarthritis pain and obstructive sleep apnea — report separately. Positive results could expand the label and the evidence base, measuring WOMAC pain scores and apnea-hypopnea index along with weight. Early topline data indicate retatrutide cut knee pain by up to 73% and reduced apnea events by up to 61%.

Safety Signals Temper Adoption

Possible Resolves by Q2 2028

Discussed by: Safety tables in the NEJM publication and clinical commentators

The 12 mg dose showed an 11.3% discontinuation rate due to adverse events and higher rates of dysesthesia (nerve-skin sensation changes) and urinary tract infections than placebo. If post-marketing surveillance finds serious safety issues, the FDA could add warnings or require a Risk Evaluation and Mitigation Strategy (REMS). The lower 4 mg dose had a discontinuation rate comparable to placebo, suggesting dose-dependent tolerability could shape real-world prescribing.

FDA Approves Retatrutide for Type 2 Diabetes

Likely Resolves by Q2 2027

Discussed by: TRIUMPH-2 data and Dr. Susan Spratt's comment in NBC News

TRIUMPH-2 showed 18.8% average weight loss and HbA1c normalization in 72% of participants on the 12 mg dose, alongside improved blood pressure and lipid profiles. If Lilly files for the diabetes indication alongside obesity, retatrutide would enter a market where GLP-1 drugs already compete on blood sugar control. Dr. Susan Spratt of Duke Health told NBC News the drug 'rivals gastric bypass surgery without the surgery.'

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

1990s onward

Roux-en-Y gastric bypass (1990s–present)

Roux-en-Y gastric bypass became the standard surgical treatment for severe obesity, typically producing 25–30% total body weight loss. For decades it was the only therapy that reliably reached that level, and it carried operative risk and a long recovery.

Then

Surgery helped people with class 3 obesity lose substantial weight, but only a small fraction of eligible patients underwent it.

Now

It set the roughly 30% weight-loss target that drug developers now aim to match without surgery.

Why this matters now

The TRIUMPH-1 press release explicitly frames 30% weight loss as "a level long associated with bariatric surgery," making surgery the comparison point for retatrutide.

2021

Semaglutide STEP trials (2021)

The STEP 1 trial, published in the New England Journal of Medicine, showed once-weekly semaglutide (Wegovy) produced about 15% average weight loss over 68 weeks in adults with obesity. It was the first GLP-1 drug to deliver weight loss at this scale without surgery.

Then

Wegovy launched as the first blockbuster obesity injection and reshaped demand for weight-loss drugs.

Now

It created the modern incretin obesity market and set a benchmark retatrutide now exceeds.

Why this matters now

Retatrutide's 28–30% weight loss roughly doubles semaglutide's results, using the same GLP-1 mechanism plus two additional hormone receptors.

2022

Tirzepatide SURMOUNT-1 trial (2022)

Lilly's SURMOUNT-1 trial of tirzepatide (Zepbound), a dual GIP/GLP-1 agonist, showed about 21% average weight loss at the 15 mg dose over 72 weeks. The results helped tirzepatide become the best-selling obesity injection.

Then

Zepbound gained FDA approval in late 2023 and outsold semaglutide on efficacy.

Now

It validated the dual-agonist approach Lilly extends with retatrutide's added glucagon receptor.

Why this matters now

Retatrutide is tirzepatide's successor: it adds glucagon receptor activation to push weight loss from about 21% toward 30%.