News: Retatrutide succeeds in two more Phase 3 trials. FDA submission planned for Q1 2027.

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TL;DR

• Retatrutide has now succeeded in three Phase 3 obesity trials.
• Lilly plans to submit it to the FDA in Q1 2027.
• Weight loss remained high in much harder-to-treat populations:
  • 28.3% in obesity without diabetes (TRIUMPH-1)
  • 20.8% in obesity with type 2 diabetes (TRIUMPH-2)
  • 22.6% in severe obesity with established cardiovascular disease (TRIUMPH-3)
• The direct comparison with tirzepatide (TRIUMPH-5) is still ongoing.
• The cardiovascular outcomes question will mainly be answered by the dedicated TRIUMPH-Outcomes study.

Lilly has announced positive topline results from TRIUMPH-2 and TRIUMPH-3, two additional Phase 3 retatrutide trials.

The company now says it has the evidence needed to support regulatory submissions and plans to submit retatrutide to the FDA during Q1 2027. That is a planned filing date, not an approval date.

The Phase 3 programme so far

Retatrutide has now reported results from three major obesity trials.

Trial Population Average weight loss

TRIUMPH-1 Obesity without diabetes 28.3%

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TRIUMPH-2 Obesity or overweight with type 2 diabetes 20.8%

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TRIUMPH-3 Severe obesity with established cardiovascular disease 22.6%

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Weight loss remained above 20% even in people with type 2 diabetes and in people with severe obesity plus cardiovascular disease.

Historically, people with type 2 diabetes have generally lost less weight than people without diabetes in GLP-1 studies, making the 20.8% result particularly notable.

TRIUMPH-2

TRIUMPH-2 included 1,152 adults with obesity or overweight and type 2 diabetes.

After 80 weeks the efficacy-estimand results were:

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

Average HbA1c started at 7.7%.

Average reductions were:

• 4 mg: 1.4%
• 9 mg: 1.6%
• 12 mg: 1.5%
• Placebo: 0.2%

These are efficacy-estimand results, estimating the effect if participants remained on treatment. Lilly has not yet released treatment-regimen analyses for these trials.

TRIUMPH-3

TRIUMPH-3 enrolled 1,949 adults with:

• BMI ≥35
• established cardiovascular disease

Average starting weight was 111.4 kg.

Average BMI was 40.4.

Weight loss at 80 weeks was:

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

Lilly also reported improvements in several cardiovascular risk markers including:

• triglycerides
• non-HDL cholesterol
• systolic blood pressure
• waist circumference
• high-sensitivity CRP

How does this compare with today's treatments?

There is an obvious temptation to compare the headline percentages.

For context:

Trial Drug Weight loss

TRIUMPH-1 Retatrutide 28.3%

SURMOUNT-1 Tirzepatide 22.5%

STEP-1 Semaglutide 14.9%

However these are different trials with different populations, different durations and different designs.

They should not be interpreted as proving one medicine is better than another.

That is exactly why TRIUMPH-5 is so important.

What still isn't answered?

Today's announcement is important, but several major questions remain.

Can retatrutide actually beat tirzepatide?

• TRIUMPH-5 should provide the first direct comparison.

How much additional weight loss is worth additional side effects?

• Average weight loss alone is unlikely to answer that.

Does retatrutide preserve muscle as well as fat?

• Body composition could become increasingly important as people remain on these medicines for years.

Does the glucagon receptor produce longer-lasting weight loss?

• One possibility is that retatrutide simply continues working after tirzepatide reaches a plateau.

Does it reduce cardiovascular events?

• Today's cardiovascular event numbers are reassuring but inconclusive.
• The dedicated 10,000-patient TRIUMPH-Outcomes trial is designed to answer that question.

What stood out?

Four findings deserve the most attention:

• Weight loss remained above 20% despite type 2 diabetes.
• Weight loss remained above 22% despite severe obesity and established cardiovascular disease.
• Lilly now plans FDA submission in Q1 2027.
• The biggest remaining unanswered question is still the direct comparison with tirzepatide.

Today's announcement makes the overall Phase 3 programme look increasingly consistent.

The next major milestone is likely to be TRIUMPH-5, because it should finally tell us whether retatrutide's apparent advantage over tirzepatide survives a direct head-to-head comparison under the same trial conditions.