Comparisons

Retatrutide vs Tirzepatide

Published Sep 12, 2026 · 7 minute read

Two Lilly molecules, one approved and one not. The trial numbers favour the newer one, with caveats that matter more than the headline.

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Key Takeaways

  • Both are Lilly molecules injected weekly. Tirzepatide hits two receptors and is approved. Retatrutide hits three and is not.
  • Phase 2 retatrutide 12 mg: 24.2% weight loss at 48 weeks. Phase 3 tirzepatide 15 mg: 20.9% at 72 weeks. Different trials, and the retatrutide curve had not flattened.
  • In type 2 diabetes, retatrutide's first phase 3 reported 15.3% weight loss at 40 weeks on 12 mg; tirzepatide's SURPASS-2 reported 11.2 kg at the same duration.
  • Lilly's TRIUMPH-4 topline claims 28.7% at 68 weeks on 12 mg, with dysesthesia in a fifth of that group. That is a press release, not a publication or a label.
  • Half-lives are close: about 5 days for tirzepatide, about 6 for retatrutide. The status gap is the real difference.
Tirzepatide Retatrutide
Receptors GIP + GLP-1 GIP + GLP-1 + glucagon
Status, September 2026 Approved as Mounjaro and Zepbound Investigational, phase 3, no label
Schedule Weekly injection Weekly injection, in trials
Half-life About 5 days (label) About 6 days (phase 1)
Best obesity result 20.9% at 72 weeks, 15 mg (phase 3) 24.2% at 48 weeks, 12 mg (phase 2)
Best type 2 diabetes result 11.2 kg at 40 weeks, 15 mg (phase 3); about 12% of the 93.7 kg baseline 15.3% at 40 weeks, 12 mg (phase 3)

What the trials showed

The obesity data come from two placebo-controlled trials of different sizes and lengths.

Weight reduction by dose: retatrutide phase 2 vs tirzepatide SURMOUNT-1Mean percent change from baseline; adults with obesity and no diabetes; different trials, different durations, not head-to-head
  • Retatrutide (phase 2, 48 wk)
  • Tirzepatide (SURMOUNT-1, 72 wk)
  • Placebo
Retatrutide 4 mg
Retatrutide (phase 2, 48 wk)
17.1%
Retatrutide 8 mg
Retatrutide (phase 2, 48 wk)
22.8%
Retatrutide 12 mg
Retatrutide (phase 2, 48 wk)
24.2%
Placebo, retatrutide trial
Placebo
2.1%
Tirzepatide 5 mg
Tirzepatide (SURMOUNT-1, 72 wk)
15%
Tirzepatide 10 mg
Tirzepatide (SURMOUNT-1, 72 wk)
19.5%
Tirzepatide 15 mg
Tirzepatide (SURMOUNT-1, 72 wk)
20.9%
Placebo, SURMOUNT-1
Placebo
3.1%

Retatrutide at 48 weeks: 4 mg 17.1%, 8 mg 22.8%, 12 mg 24.2%, placebo 2.1%. Tirzepatide at 72 weeks: 5 mg 15.0%, 10 mg 19.5%, 15 mg 20.9%, placebo 3.1%.

Source: Jastreboff 2023 (retatrutide); Jastreboff 2022 (SURMOUNT-1)

83%of participants on retatrutide 12 mg lost at least 15% of body weight at 48 weeks, versus 2% on placebo.
57%of participants on tirzepatide 15 mg lost at least 20% at 72 weeks in SURMOUNT-1, versus 3% on placebo.
338 vs 2,539participants: the retatrutide phase 2 trial against SURMOUNT-1. Phase 2 numbers are estimates with wide intervals.

Three cautions. The retatrutide trial ran 48 weeks and its weight curve had not flattened at the end, so 24.2% is a point on a falling line, not a plateau. SURMOUNT-1 ran 72 weeks, closer to a plateau. And a lower starting dose (2 mg rather than 4 mg) reduced gastrointestinal side effects for retatrutide, so the tolerability picture depends on escalation as much as on the target dose.

In type 2 diabetes, both molecules have 40-week data. Retatrutide’s first phase 3, as monotherapy, is published.

Weight reduction in type 2 diabetes: retatrutide phase 3 monotherapyMean percent change from baseline at 40 weeks vs placebo. Tirzepatide's 40-week diabetes result, from SURPASS-2, is given in the text
  • Retatrutide
  • Placebo
4 mg
Retatrutide
11.5%
Placebo
2.6%
9 mg
Retatrutide
13.9%
Placebo
2.6%
12 mg
Retatrutide
15.3%
Placebo
2.6%

Retatrutide monotherapy at 40 weeks: 4 mg 11.5%, 9 mg 13.9%, 12 mg 15.3%, placebo 2.6%.

Source: Retatrutide phase 3 monotherapy in type 2 diabetes, Lancet 2026

Discontinuation for adverse events was 2 to 5% on retatrutide and 0% on placebo. For comparison, SURPASS-2 reported 7.6, 9.3, and 11.2 kg of weight loss on tirzepatide 5, 10, and 15 mg over the same 40 weeks, against 5.7 kg on semaglutide 1 mg, and tirzepatide beat semaglutide on HbA1c at every dose. The two trials had different comparators and populations, so the chart and the kilograms are not a head-to-head.

Lilly has also reported phase 3 topline results in obesity. TRIUMPH-4 randomised 445 adults with obesity and knee osteoarthritis to retatrutide 9 mg, 12 mg, or placebo for 68 weeks, and reported mean weight loss of 26.4% and 28.7% against 2.1%. It also reported dysesthesia, altered skin sensation, in 20.9% of the 12 mg group versus 0.7% on placebo, the same signal semaglutide 7.2 mg showed in STEP UP. All of that is a press release. It has not been peer-reviewed and is not on any label, and this page treats it as company figures.

What the third receptor adds

Tirzepatide activates the GIP and GLP-1 receptors. Both reduce appetite and slow gastric emptying. Retatrutide adds the glucagon receptor, which raises energy expenditure and drives fat oxidation in the liver. In a phase 2a trial in metabolic dysfunction-associated steatotic liver disease, retatrutide reduced liver fat by more than 80% at the higher doses over 24 weeks.

Glucagon activity has costs. Retatrutide’s phase 2 reported dose-dependent heart rate increases that peaked at 24 weeks and declined after, and glucagon can raise glucose, which the GLP-1 and GIP components have to offset. Characterising that balance is what phase 3 is for. The GLP-1 vs GLP-2 vs GLP-3 page explains the single, dual, and triple naming, and why “GLP-3” is not a hormone.

Pharmacokinetics

Both are engineered for weekly dosing with a fatty-acid side chain that binds albumin and slows clearance.

Half-life Time to about 97% of steady state Source
Tirzepatide About 5 days (120 hours) About 25 days FDA label
Retatrutide About 6 days (144 hours) About 30 days Phase 1 publication

The practical behaviour is the same: levels build over the first month, each dose step takes about four weeks to settle, and the drug takes about a month to clear after the last dose. The half-life visualizer models both.

The status gap is the real difference

Tirzepatide has two labels, six approved dose steps, a cardiovascular outcomes trial, and four years of post-marketing experience. Retatrutide has a phase 3 program and a press release. Until a label exists, there is no approved dose, no approved escalation, no approved indication, and no product a pharmacy can dispense.

Which comparison you wanted

If you log tirzepatide, the entry is product, date, milligrams, and site. How GLP-1 tracking works covers what to record.

6. Retatrutide vs Tirzepatide FAQ

  • Is retatrutide better than tirzepatide?

    The two have not been compared head-to-head. In separate trials, retatrutide's phase 2 result, 24.2% at 48 weeks, exceeds tirzepatide's phase 3 result, 20.9% at 72 weeks. Phase 2 trials are smaller and shorter, and the retatrutide curve was still falling at the endpoint, so the numbers describe different points on different curves.

  • What does the third receptor do?

    Glucagon receptor activity raises energy expenditure and liver fat oxidation, on top of the appetite effects of GLP-1 and GIP. It also tends to raise heart rate and can raise glucose, which is why the safety profile of the glucagon component is a focus of phase 3.

  • When will retatrutide be approved?

    It is in phase 3 with no filed application disclosed and no approved label as of September 2026. Timelines are Lilly's to announce. This page does not predict approval.

  • Is retatrutide GLP-3?

    No. GLP-3 is not a hormone. Retatrutide is a triple agonist at the GIP, GLP-1, and glucagon receptors. The nickname comes from counting receptors, not from any molecule called GLP-3.

  • Can I get retatrutide?

    Not as an approved medicine. Products sold online as retatrutide are unapproved and untested, and this page does not cover sourcing. Tirzepatide is available by prescription as Mounjaro and Zepbound.

7. Sources

References used for this article

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