Retatrutide vs semaglutide: trial results, dosing and status

Semaglutide is the GLP-1 drug behind Wegovy and Ozempic, approved in the United States since 2017. Retatrutide is Eli Lilly’s investigational triple agonist, which has finished several Phase 3 trials but has not been approved anywhere. People compare them because retatrutide’s trial weight loss is the largest reported so far. The table below lines up the published facts. Retatrutide figures come from Lilly releases and journal abstracts; semaglutide figures come from the FDA labels and the STEP 1 paper. Full profiles are on the retatrutide hub and the semaglutide hub.

Side-by-side comparison table

Sources: TRIUMPH-1 (Eli Lilly, May 21, 2026) (N Engl J Med, Sep 29, 2026), retatrutide half-life (The Lancet, Oct 27, 2022), retatrutide time to peak from Lilly’s protocol summary (Eli Lilly, hosted on ClinicalTrials.gov, Aug 29, 2022), ladder (Eli Lilly, Dec 11, 2025), Wegovy label (Novo Nordisk, Jun 18, 2026), STEP 1 (New England Journal of Medicine, Mar 18, 2021).

STEP 1 used a treatment-policy estimand and TRIUMPH-1’s journal analysis used a treatment-regimen estimand. Both count every randomized participant whether or not they stayed on the drug, so −25.0% and −14.9% are the closest like-for-like pair. Lilly’s press releases lead with the efficacy estimand (−28.3%), which assumes everyone stayed on treatment and is usually 1 to 3 points larger.

Why the numbers are not directly comparable

• Length. 80 weeks for TRIUMPH-1 vs 68 weeks for STEP 1. Twelve extra weeks of treatment can add weight loss on their own.
• Era and population. STEP 1 was published in 2021 and TRIUMPH-1 in 2026. Both excluded people with diabetes, but baseline weights, regions and background care differ. TRIUMPH-1 participants averaged 112.7 kg and a BMI of 40.0 (Eli Lilly, May 21, 2026).
• Analysis details. Missing-data handling differs between sponsors even within ITT-style estimands.
• Side-effect sources. Retatrutide rates are Lilly’s 80-week topline from one trial; Wegovy rates come from a label table pooling three trials of up to 68 weeks.

A fair one-line summary: retatrutide’s trial results are larger, but there is no randomized evidence yet on how the two compare in the same people.

Is there a head-to-head trial?

Not in obesity, as far as the registry shows. Lilly lists a type 2 diabetes trial comparing retatrutide with semaglutide (NCT06260722); it was active, not recruiting on ClinicalTrials.gov in October 2026 and has no results. The retatrutide head-to-head obesity trial, TRIUMPH-5, compares it with tirzepatide, not semaglutide (see retatrutide vs tirzepatide).

The closest published data come from retatrutide’s Phase 2 diabetes trial, which included dulaglutide 1.5 mg, a different weekly GLP-1 receptor agonist, as an active comparator (The Lancet, Jun 26, 2023).

Dulaglutide is not semaglutide, so this table says something about retatrutide vs an older GLP-1 drug, not about Wegovy or Ozempic.

Mechanism: one receptor vs three

Semaglutide mimics GLP-1, a gut hormone released after meals. The Wegovy label describes it as a GLP-1 receptor agonist (Novo Nordisk, Jun 18, 2026).

Retatrutide acts on the same GLP-1 receptor plus two more: the GIP receptor (another meal-related gut hormone, the second target of tirzepatide) and the glucagon receptor. In laboratory testing it showed balanced glucagon and GLP-1 receptor activity with more GIP receptor activity (Cell Metabolism, Aug 18, 2022). Because it hits three receptors, sellers of unapproved products sometimes call it “GLP-3”; FDA warning letters quote that name (FDA, Aug 24, 2026). It is a nickname, not a hormone. See GLP-3 vs GLP-1.

Dose ladders

Both ladders step up every 4 weeks. Retatrutide’s is the Phase 3 trial protocol, reported as published facts, not a recommendation. Wegovy’s is the FDA label; ask your prescriber about any semaglutide dose.

• Weekly dose (published steps)
• Modeled amount (mg-eq)
• Stable window

• Weekly dose (published steps)
• Modeled amount (mg-eq)
• Stable window

The milligram numbers are not comparable across molecules. Each peptide has its own potency at each receptor, so 2.4 mg of semaglutide and 12 mg of retatrutide are simply the top doses each program chose. The retatrutide titration tool and the semaglutide titration tool lay out each ladder by date.

Half-life and accumulation

Semaglutide has the slightly longer half-life: about 1 week vs about 6 days. The Wegovy label says semaglutide remains in circulation for about 5 to 7 weeks after the last dose (Novo Nordisk, Jun 18, 2026).

These are modeled relative amounts, not blood levels. Plot them in the retatrutide plotter and the semaglutide plotter, or overlay both in the multi-compound plotter.

Side effects compared

Sources: (Eli Lilly, May 21, 2026) (Novo Nordisk, Jun 18, 2026)

Gastrointestinal rates look broadly similar. The clearer difference is dysesthesia, an abnormal skin sensation such as tingling, burning or skin sensitivity. It was 12.5% on retatrutide 12 mg in TRIUMPH-1 and 20.9% in the knee osteoarthritis trial TRIUMPH-4 (Eli Lilly, Dec 11, 2025). It is not unique to retatrutide, though: in the Wegovy HD trials it was 22% on semaglutide 7.2 mg vs 6% on 2.4 mg and 0% on placebo (Novo Nordisk, Jun 18, 2026). So the signal is not unique to one molecule, and it appeared at the highest doses of both.

Higher-dose semaglutide

Wegovy HD 7.2 mg was approved on Mar 19, 2026 (FDA, Mar 19, 2026). In the label’s Study 8, weight change at 72 weeks was −18.8% on 7.2 mg, −15.5% on 2.4 mg and −3.9% on placebo (least-squares mean, intent-to-treat) (Novo Nordisk, Jun 18, 2026). That narrows the gap to retatrutide’s trial figures, but it is still a separate trial with its own population.

Heart outcomes

Semaglutide has a proven cardiovascular benefit. In SELECT, 17,604 adults with heart disease and overweight or obesity had major cardiovascular events in 6.5% on semaglutide vs 8.0% on placebo, a hazard ratio of 0.80 (New England Journal of Medicine, Dec 14, 2023).

Retatrutide has no outcome result yet. TRIUMPH-3, in people with severe obesity and heart disease, reported a three-part major cardiovascular event hazard ratio of 1.12 (95% CI 0.64 to 1.96) from 27 vs 23 events (Eli Lilly, Jul 23, 2026). The trial was not designed to test this, and the wide interval means the result is inconclusive in either direction. A dedicated cardiovascular and kidney outcomes trial is running.

Status

Ozempic was approved on Dec 5, 2017 (FDA, Oct 19, 2026) and Wegovy on Jun 4, 2021 (FDA, Oct 19, 2026). Retatrutide is not approved by any regulator (Eli Lilly, Aug 12, 2026); Lilly plans a U.S. submission in the first quarter of 2027 (Eli Lilly, Sep 29, 2026). Lilly states that retatrutide cannot be legally sold or marketed for human use, so products sold online under that name are not the trial drug. For the approval timeline, see is retatrutide FDA approved.