Retatrutide reports up to 30.3% average weight loss in TRIUMPH-1

Eli Lilly reported topline Phase 3 results showing that retatrutide, an investigational once-weekly injection that activates three hormone receptors, produced average weight loss of 28.3% at 80 weeks and up to 30.3% after two years in adults with obesity or overweight who did not have diabetes ^[1]. All three doses studied met the trial's primary and key secondary endpoints ^[1]. The drug is still experimental and has not been approved by the FDA.

Retatrutide works on receptors for GIP, GLP-1 and glucagon — one more target than tirzepatide (Mounjaro/Zepbound), which hits GIP and GLP-1, and two more than semaglutide (Ozempic/Wegovy/Rybelsus), which acts on GLP-1 alone ^[1]. The randomized, double-blind, placebo-controlled TRIUMPH-1 master trial enrolled 2,339 participants with obesity or overweight plus at least one weight-related health condition ^[1].

The numbers

At 80 weeks, people on the highest dose (12 mg) lost an average of 70.3 pounds, or 28.3%, from an average starting weight of 248.5 pounds and an average body mass index of 40.0 ^[1]. In that group, 45.3% lost at least 30% of their body weight — a level historically linked with bariatric surgery — and 65.3% dropped below the BMI 30 threshold that defines obesity, including 37.5% of those who started with a BMI of 40 or higher ^[1].

Lower doses also produced large reductions: 64.4 pounds (25.9%) on 9 mg and 47.2 pounds (19.0%) on 4 mg, which requires only one titration step up from the 2 mg starting dose ^[1].

A prespecified blinded extension followed 532 participants with a starting BMI of at least 35 who tolerated their assigned treatment out to 104 weeks, with everyone reaching a maximum tolerated dose of 9 mg or 12 mg ^[1]. Those originally assigned to 12 mg lost an average of 85.0 pounds by week 104, a 30.3% reduction from an average baseline of 268.3 pounds and a BMI of 42.8 ^[1].

Lilly also reported cardiometabolic changes: the 12 mg group's waist circumference fell by an average of 24.1 cm (9.5 inches), with improvements in non-HDL cholesterol, triglycerides, systolic blood pressure and the inflammation marker hs-CRP ^[1].

Side effects rose with dose

Side effects looked like those seen with other incretin drugs and were mostly gastrointestinal. Across the 4, 9 and 12 mg groups, nausea was reported by 28.6%, 38.4% and 42.4% of participants versus 14.8% on placebo; diarrhea by 25.2%, 34.1% and 32.0% versus 13.5%; constipation by 23.8%, 25.9% and 26.1% versus 10.9%; and vomiting by 10.6%, 22.8% and 25.3% versus 4.8% ^[1].

Other reported events included upper respiratory infections, urinary tract infections and mild to moderate dysesthesia — abnormal skin sensations — with most urinary and neurological cases resolving during treatment ^[1]. In Lilly's earlier TRIUMPH-4 trial in people with obesity and knee osteoarthritis, dysesthesia was reported in up to 20.9% of participants at the 12 mg dose and was described as generally mild ^[2].

Dropouts from side effects tracked with dose: 4.1% on 4 mg, 6.9% on 9 mg and 11.3% on 12 mg, compared with 4.9% on placebo ^[1].

Why it matters for patients

These are the largest average weight-loss figures yet reported from a Phase 3 obesity trial, and they come from a company press release rather than a peer-reviewed publication, so the full data set has not been independently scrutinized ^[1]. A 2025 review of 26 randomized trials in 15,491 adults without diabetes had projected 24.2% weight loss for retatrutide at 12 mg, ahead of tirzepatide (17.8%) and injected semaglutide (13.9%) ^[1].

The dose-by-dose results also show the trade-off patients and clinicians already face with GLP-1 drugs: the biggest reductions came with the most nausea, vomiting and the highest rate of stopping treatment ^[1]. The 4 mg dose still produced 19.0% average loss with a discontinuation rate slightly below placebo ^[1].

What is not yet known: whether retatrutide will be approved, when, what it would cost, whether insurers would cover it, and how weight loss holds up after stopping. Head-to-head trials against tirzepatide or semaglutide were not described in these sources.

What happens next

Lilly said it planned to present detailed TRIUMPH-1 data at the 86th annual American Diabetes Association Scientific Sessions ^[1]. Results from TRIUMPH-2 in people with type 2 diabetes and TRIUMPH-3 in people with established cardiovascular disease were expected later in 2026 ^[1]. In December 2025, Lilly said seven additional Phase 3 readouts were expected in 2026, including studies of maintenance dosing, with other trials covering obstructive sleep apnea and knee osteoarthritis ^[2].