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Retatrutide TRIUMPH-2 and TRIUMPH-3: What Lilly Reported in July 2026

Published October 17, 2026 · 7 min read

The short version

On July 23, 2026, Eli Lilly announced topline results from two more Phase 3 trials of retatrutide, a once-weekly injectable drug that acts on three hormone receptors (GIP, GLP-1 and glucagon). TRIUMPH-2 enrolled adults with type 2 diabetes and obesity or overweight. TRIUMPH-3 enrolled adults with severe obesity and established cardiovascular disease. Both met their primary endpoints, with average weight loss at 80 weeks of up to 20.8% in TRIUMPH-2 and up to 22.6% in TRIUMPH-3, compared with 4.0% and 3.2% on placebo. Gastrointestinal side effects and a sensation disturbance called dysesthesia were more common on retatrutide. The cardiovascular outcome numbers were inconclusive. Lilly says it plans to submit an application to the FDA in the first quarter of 2027.

Where these trials fit

These results are part of the TRIUMPH Phase 3 program. Earlier reports covered TRIUMPH-4, in adults with obesity and knee osteoarthritis (announced December 11, 2025), and TRIUMPH-1, in adults with obesity and no diabetes (announced May 21, 2026); the latter is covered in our earlier article on the Phase 2 and Phase 3 data. Lilly now describes retatrutide as having produced positive results in five Phase 3 studies. Each trial enrolled a different population, which matters when comparing numbers across them.

TRIUMPH-2: type 2 diabetes with obesity or overweight

TRIUMPH-2 (NCT05929079) was an 80-week, randomized, double-blind, placebo-controlled trial of 1,152 adults, assigned in equal numbers to three retatrutide dose arms (4 mg, 9 mg and 12 mg once weekly) or placebo. At baseline, participants averaged 106.4 kg (about 235 lb), a body mass index of 38.2 and an A1C of 7.7%. A1C is a blood-test measure of average blood sugar over the previous few months.

Using the efficacy estimand, which counts what happened in participants who stayed on the study drug and did not use other weight-management treatment, average weight change at 80 weeks was:

• 4 mg: −12.7%
• 9 mg: −19.1%
• 12 mg: −20.8%
• Placebo: −4.0%

A1C fell by 1.4 percentage points (4 mg), 1.6 (9 mg) and 1.5 (12 mg), compared with 0.2 on placebo.

TRIUMPH-3: severe obesity with cardiovascular disease

TRIUMPH-3 (NCT05882045) was also an 80-week, randomized, double-blind, placebo-controlled trial. It enrolled 1,949 adults with a body mass index of 35 or higher and established cardiovascular disease, with or without type 2 diabetes, assigned 1:1:2 to retatrutide 9 mg, 12 mg or placebo. Baseline weight averaged 111.4 kg (about 246 lb) and body mass index averaged 40.4.

• 9 mg: −21.6%
• 12 mg: −22.6%
• Placebo: −3.2%

At the highest dose arm, Lilly also reported changes in several cardiometabolic markers: triglycerides down 37.0%, non-HDL cholesterol down 16.5%, systolic blood pressure down 9.3 mmHg, waist circumference down 7.5 inches and hsCRP, an inflammation marker, down 51.2%.

The cardiovascular events: what the numbers do and do not show

TRIUMPH-3 also counted major adverse cardiovascular events (MACE), comparing the two retatrutide arms pooled against placebo. Lilly reported two versions:

• MACE-5 (death from any cause, heart attack, stroke, heart failure event or coronary revascularization): 44 events on retatrutide versus 52 on placebo, hazard ratio 0.82 (95% confidence interval 0.55 to 1.22).
• MACE-3 (cardiovascular death, heart attack or stroke): 27 events versus 23, hazard ratio 1.12 (95% confidence interval 0.64 to 1.96).

A hazard ratio below 1.0 means fewer events in the treated group, and above 1.0 means more. Both confidence intervals include 1.0, so these results are compatible with a benefit, no difference, or a harm. With only a few dozen events in each analysis, the intervals are wide. The release also gave on-treatment analyses that were not pre-specified, with hazard ratios of 0.73 for MACE-5 and 0.92 for MACE-3; analyses like that are more open to bias, because they exclude events after people stop the drug. This is a good example of why a weight-loss result and a cardiovascular-outcome result are separate questions.

Reported side effects

Lilly said the common adverse events were generally mild to moderate and mostly resolved during treatment. The rates below are the percentage of participants in each arm reporting the event.

Dysesthesia is an abnormal skin sensation, such as tingling or sensitivity to touch. It has appeared in earlier retatrutide trials too, and Lilly described it as mostly mild to moderate. Hyperglycemia was less common on retatrutide than on placebo in TRIUMPH-3 (3.1 to 3.9% versus 13.4%).

The share of participants who stopped treatment because of an adverse event rose with the higher dose arms in TRIUMPH-3 and was uneven across arms in TRIUMPH-2:

• TRIUMPH-2: 3.8% (4 mg), 11.6% (9 mg), 7.7% (12 mg), versus 4.9% on placebo.
• TRIUMPH-3: 9.8% (9 mg), 13.5% (12 mg), versus 4.8% on placebo.

What the announcement does not tell us

• Only one way of counting weight loss was reported. The release gave efficacy-estimand results. It did not give the treatment-regimen estimand, which includes everyone as randomized regardless of whether they stayed on treatment and usually produces smaller numbers (see our guide to reading trial results).
• No serious adverse event rates were given in the release as reviewed, and no breakdown of the reasons behind the discontinuations.
• No threshold figures, such as the share of participants losing at least 20% of body weight, and no share of participants reaching an A1C of 6.5% or lower.
• No peer review yet. Lilly says full results will be presented at future medical meetings and published in peer-reviewed journals. Numbers can shift when the complete data are scrutinized.

Reading across the trials

It is tempting to line up 20.8%, 22.6% and the 28.3% reported earlier for TRIUMPH-1 and rank the populations. The trials enrolled different people (with and without diabetes, with and without cardiovascular disease), had different baseline weights and used different dose arms, so they were not designed to be compared head to head. A more defensible comparison is within each trial: in TRIUMPH-3, the 12 mg arm averaged 22.6% weight loss against 3.2% for placebo, a gap of 19.4 percentage points; in TRIUMPH-2, the figures were 20.8% against 4.0%, a gap of 16.8 points. Those gaps are simple subtraction by this article, not figures reported by the sponsor.

What happens next

Lilly said it is completing the manufacturing and quality documentation needed for a Biologics License Application and plans to submit it to the FDA in the first quarter of 2027. It said it has the clinical data to support submissions for obesity, knee osteoarthritis pain and obstructive sleep apnea, and that further Phase 3 studies continue in areas including chronic low back pain, cardiovascular and renal outcomes, and fatty liver disease. A submission is not an approval, and the FDA has not made any decision about retatrutide. Until then, the drug remains investigational.

Sources

• Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Press release, July 23, 2026.
• AJMC. Retatrutide Achieves Up to 30.3% Average Weight Loss in Phase 3 TRIUMPH-1 Trial.
• Patient Care Online. Retatrutide Achieves Up to 28.7% Weight Loss and Marked Knee Pain Reduction in Phase 3 TRIUMPH-4 Trial.

Related reading

• Retatrutide Trial Results Explained: What the Phase 2 and Phase 3 Data Show
• How to Read a Clinical Trial Result
• Why “It Worked for Me” Isn’t Evidence
• Glossary

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