What is retatrutide?

What is retatrutide?

Retatrutide is a synthetic triple-agonist peptide that acts simultaneously on the GIP, GLP-1 and glucagon receptors. It is supplied for research purposes in a pre-filled multi-dose injection pen.

It is studied in weight-loss and metabolism research, where its three-receptor design has shown the largest reductions within the incretin class in published studies. Results vary from study to study with dose and duration.

Mechanism of action

Retatrutide (LY3437943) is an acylated, once-weekly peptide that activates three receptors of the incretin and glucagon family at the same time. The GLP-1 part slows gastric emptying, increases satiety and enhances glucose-dependent insulin secretion. The GIP part acts on the adipocyte and, according to the dual-agonist data, softens the gastrointestinal tolerance ceiling that limits pure GLP-1 agonists.

The third arm, the glucagon receptor, is what sets retatrutide apart from semaglutide and tirzepatide: glucagon agonism increases hepatic lipid oxidation and energy expenditure, so weight loss does not depend on eating less alone. That same arm is why the published titration curves cannot be extrapolated from the dual agonists.

In the phase 2 trials, administration was a weekly subcutaneous injection with dose steps lasting several weeks, because the gastrointestinal effects depend mainly on the speed of the climb rather than on the final dose.

What the published research says

1. 1.
   Jastreboff et al., N Engl J Med, 2023PMID 37366315

   Phase 2 trial in 338 adults with obesity, 48 weeks. Mean weight reduction was 24.2% with 12 mg weekly against 2.1% with placebo, with adverse effects that were mostly gastrointestinal, mild or moderate, and tied to titration.

2. 2.
   Jastreboff et al., N Engl J Med, 2026 (TRIUMPH-1)PMID 42814954

   Phase 3 trial in 2,339 adults with obesity without diabetes, 80 weeks. Mean weight reduction was 17.6%, 23.7% and 25.0% with 4, 9 and 12 mg weekly against 3.9% with placebo, with adverse effects that were mostly gastrointestinal. These are the first published results of the phase 3 programme; the compound remains unauthorised.

3. 3.
   Rosenstock et al., Lancet, 2023PMID 37385280

   Phase 2 in type 2 diabetes, 36 weeks. At the highest doses HbA1c fell by close to 2 points and weight by around 17%, with the same gastrointestinal profile as in obesity.

4. 4.
   Jastreboff et al., N Engl J Med, 2022 (tirzepatide, reference)PMID 35658024

   SURMOUNT-1, the dual-agonist trial retatrutide is compared against: 20.9% weight loss with 15 mg at 72 weeks. It serves as the scale for reading the triple-agonist data.

What side effects does retatrutide have?

• Nausea and reduced appetite: the most reported effects in the research literature, which usually settle with slow titration.
• Other gastrointestinal effects (fullness, constipation or loose stools) reported at higher doses.
• Mild, transient injection-site reactions.

How is retatrutide dosed?

It is dosed once a week and titrated slowly upwards: a common research progression is 2 → 4 → 8 mg, holding each step for about four weeks, with a maximum of 12 mg a week. The multi-dose pen sets any of those steps directly, so there is no measuring or mixing.

Storing the pen

Keep the pen between 2 and 8 °C, protected from light and never frozen. Unopened it has a 24-month shelf life; from the first puncture, 12 months. If no fridge is available it keeps for up to 30 days at room temperature, below 30 °C. Let it reach room temperature before giving a dose. The dial sets each dose directly in milligrams: there is no reconstitution, no bacteriostatic water and no volume calculation.

How do you get retatrutide?

Body Pharm supplies retatrutide in Spain in a sealed, HPLC-verified pen, with a published certificate of analysis (CoA) and discreet delivery. It is sold exclusively for research and analytical purposes.

How much does retatrutide cost per month?

≈ 249 € a month at the usual research dose of 8 mg a week: one 32 mg pen covers about four weeks. The 64 mg pen lowers the cost per mg.

How it compares

Against semaglutide (a single receptor, GLP-1) and tirzepatide (two receptors, GIP and GLP-1), retatrutide adds glucagon. In the published data that translates into the largest weight reduction of the class: 24.2% at 48 weeks in phase 2 and 25.0% at 80 weeks in the phase 3 TRIUMPH-1 trial, published in 2026, at the price of an absence of cardiovascular outcome data and of authorisation as a medicine. Semaglutide and tirzepatide have years of cardiovascular outcome trials behind them; retatrutide does not.

For a research protocol, the practical difference is in the titration: the published retatrutide schedule climbs more slowly than tirzepatide's, and the maximum dose studied is 12 mg weekly.

• Retatrutide vs semaglutide vs tirzepatide
• Retatrutide 64 pen (large format)
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