Retatrutide's Phase 3 Results Are Now in NEJM and The Lancet. The Drug Is Still Unapproved

What happened / Why it matters

What happened. Two large phase 3 trials of retatrutide, Eli Lilly’s investigational once-weekly injection, have now been published in peer-reviewed journals: TRIUMPH-1 in the New England Journal of Medicine and TRIUMPH-2 in The Lancet. Both found large average weight loss over 80 weeks compared with placebo.

Why it matters. Retatrutide is a “triple agonist”: it acts on three hormone receptors (GIP, GLP-1 and glucagon). But it is not FDA-approved for any use, FDA says it cannot be used in compounding under federal law, and the headline numbers you may have seen from the company are not the same as the numbers in the journals. This article covers what the trials found, what the differences in the figures mean, and what is still unknown.

What did TRIUMPH-1 and TRIUMPH-2 find?

Both trials were randomized and placebo-controlled. Doses are reported here as low, medium and high.

In TRIUMPH-1, the NEJM report also describes two subgroups: people with knee osteoarthritis (574 participants) had larger improvements in knee pain scores than placebo, and people with obstructive sleep apnea (243) had larger reductions in the apnea-hypopnea index.

Another phase 3 trial, TRANSCEND-T2D-1, tested retatrutide in 537 adults with type 2 diabetes not on other treatment. Over 40 weeks it reported HbA1c reductions of 0.88 to 1.12 percentage points versus placebo and weight loss of 11.5% to 15.3% versus 2.6%.

Earlier, a phase 2 trial in NEJM with 338 participants reported weight loss of up to 24.2% at 48 weeks versus 2.1% with placebo.

Why do Lilly’s numbers differ from the journal’s?

For TRIUMPH-1, Lilly’s May release gives 28.3% on the highest dose; NEJM reports 25.0%. For TRIUMPH-2, Lilly’s September release gives 20.8%; The Lancet reports 18.8%.

The reason is a statistical choice. Lilly labels its figures the “efficacy estimand,” which it defines as the effect had all randomized participants remained on treatment. The journal figures use the treatment-regimen estimand, which Lilly describes as the average effect regardless of whether people kept taking the drug or started prohibited weight-loss treatments. Lilly’s May release gives the same 25.0% under that estimand. Neither is wrong, and they answer different questions.

Two practical rules follow:

• Treat the journal figure as the primary one. When a company figure is quoted, check which estimand it uses.
• Do not compare a company figure such as 28.3% with a figure from another drug’s trial that uses a different analysis. They are not measuring the same thing, and trials in different populations are not a head-to-head comparison.

One trial against an approved drug is so far company-reported only. On Oct. 28, Lilly reported topline results from an open-label trial in adults with type 2 diabetes, comparing retatrutide with Ozempic at its highest dose for diabetes (2 mg). Under the company’s efficacy analysis, which estimates the effect had all participants stayed on treatment, A1C fell 2.2 points on retatrutide versus 1.8 on Ozempic, and weight fell 19.5% to 20.9% versus 9.4%. The results have not been published in a peer-reviewed journal, and they come from people with diabetes, so they do not compare retatrutide with Wegovy for obesity. We are not reporting figures from other trials that are known only through company announcements or secondary coverage.

What side effects did the trials report?

Retatrutide has no approved label, so the safety information below comes only from the trials.

• Stomach and gut effects rose with dose. In TRIUMPH-2, nausea was reported by 14%, 21% and 28% of participants at the low, medium and high doses, versus 8% on placebo.
• Low blood pressure was reported in up to 6% of retatrutide participants versus under 1% on placebo, and dysesthesia (abnormal skin sensations) in up to 7% versus 1%, in the same trial.
• Stopping because of side effects or death was 4%, 12% and 8% at the low, medium and high doses in TRIUMPH-2, versus 5% on placebo. For TRIUMPH-1, a figure we have only from the company, Lilly reports stopping because of side effects at 4.1%, 6.9% and 11.3%, versus 4.9% on placebo.
• Deaths: six across the three retatrutide groups and one in the placebo group in TRIUMPH-2; the investigators deemed them unrelated to the treatment.
• Heart rate rose in a dose-dependent way in the phase 2 trial, peaking at 24 weeks.
• Long-term safety is unknown. The cardiovascular and renal outcomes trial, NCT06383390, has a planned enrollment of 10,000 and is active but no longer recruiting.

What is retatrutide’s regulatory status?

• Not approved. A search of FDA’s Drugs@FDA data on Oct. 30 found no product listed under that name. Lilly says it plans to submit an application to FDA in the first quarter of 2027. That is a company plan, not a decision or a timeline FDA has accepted.
• Not allowed in compounding. FDA states that retatrutide and cagrilintide “cannot be used in compounding under federal law” and “have not been found safe and effective for any condition.” The same page describes FDA warnings to telehealth companies, API distributors and outsourcing facilities. The HHS interim policy published today covers six other peptides and does not include retatrutide.
• There is no FDA-approved version to buy. FDA says retatrutide is not a component of any FDA-approved drug. We do not link to or recommend sellers.

What happens next?

The open questions are approval and long-term safety. An FDA decision requires an application first, and the cardiovascular and renal outcomes trial has not reported. Until then, there is no FDA-approved retatrutide product. Anyone considering their options for weight loss should talk with a clinician about approved treatments and the evidence for each.

Regulatory status verified Oct. 31, 2026.