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Retatrutide’s Phase 3 results: what four trials showed

Lilly’s triple-agonist produced average weight loss approaching 30% in its pivotal trials. A look at the numbers, the side effects, and the timeline to approval.

Published

Summaries of published research for educational discussion. Not medical advice.

Retatrutide is Eli Lilly’s experimental weight-loss drug and the most talked-about peptide of 2026. Between December 2025 and July 2026, Lilly reported results from four large Phase 3 trials, and the numbers are the biggest yet seen for a weight-loss medication. Here is what those trials showed, what the trade-offs look like, and where things stand.

What makes it different

Semaglutide (Wegovy) acts on one hormone receptor, GLP-1. Tirzepatide (Zepbound) acts on two, GLP-1 and GIP. Retatrutide adds a third: the glucagon receptor. GLP-1 and GIP mainly reduce appetite and improve blood sugar control. Glucagon signaling is thought to raise energy expenditure and help the liver burn fat, which may explain why the weight loss runs deeper than with the earlier drugs.

The Phase 3 results so far

Each trial tested up to three dose levels against placebo. The figures below are average weight loss for the highest dose, measured in people who stayed on treatment.

TrialWho was in itLengthRetatrutidePlacebo
TRIUMPH-4Obesity and knee osteoarthritis (445 people)68 weeks28.7%2.1%
TRIUMPH-1Obesity or overweight with a related condition, no diabetes (2,339)80 weeks28.3%2.2%
TRIUMPH-3Severe obesity and heart disease (1,949)80 weeks22.6%3.2%
TRIUMPH-2Type 2 diabetes and obesity or overweight (1,152)80 weeks20.8%4.0%

A few details stand out:

  • Extended treatment went further. In a TRIUMPH-1 extension, people on the highest dose who continued to 104 weeks averaged about 30% weight loss.
  • Many people lost a quarter of their weight or more. In TRIUMPH-1, about 63% of people on the highest dose lost at least 25% of their body weight, and about 45% lost at least 30%.
  • Knee pain improved. In TRIUMPH-4, roughly 70% of people on the two higher doses reported their knee pain had fallen by 70% or more, compared with about a quarter on placebo.
  • Diabetes results were smaller but still large. As with other drugs in this class, people with type 2 diabetes lost less weight. Their A1C (a measure of long-term blood sugar) fell by up to 1.6 percentage points.

Side effects and trade-offs

  • Digestive side effects were the most common: nausea, diarrhea, constipation, vomiting, and reduced appetite, as with other GLP-1 drugs.
  • Dysesthesia, an abnormal skin sensation such as tingling or burning, showed up far more often than with earlier drugs. In TRIUMPH-4 it affected about 21% of people on the highest dose versus under 1% on placebo, though most cases were mild.
  • More people stopped treatment at higher doses. In TRIUMPH-4, 18% on the highest dose quit because of side effects, versus 4% on placebo. Some stopped because they felt they were losing too much weight.
  • Long-term questions remain. These trials don’t yet show how much of the weight lost is muscle, what happens after stopping, or whether the drug reduces heart attacks and strokes. Those answers will come from longer studies.

Where it stands

Retatrutide isn’t approved anywhere. Lilly has said it plans to apply for FDA approval in the first quarter of 2027, which would put a decision around late 2027 or 2028. Anything sold as “retatrutide” before then is unregulated, so its identity, purity, and dose can’t be assumed. That is exactly why members share and compare lab results on the forum.

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