Phase 3 (ongoing)Weight lossMetabolic

Retatrutide

LY3437943 · "triple agonist", GIP, GLP-1 and glucagon receptors

Overview

Retatrutide (LY3437943) is an investigational triple receptor agonist from Eli Lilly that activates the GIP, GLP-1 and glucagon receptors. In a phase 2 trial it produced roughly 24% weight loss at 48 weeks at the top dose, the largest seen in an obesity drug to date. It is not approved anywhere; phase 3 trials are ongoing.

01 What is Retatrutide?

In plain English.

Retatrutide is an experimental once-weekly injection being developed by Eli Lilly for obesity, type 2 diabetes and related metabolic conditions. It belongs to the same broad family as semaglutide (Wegovy / Ozempic) and tirzepatide (Mounjaro / Zepbound), but goes one step further: it acts on three gut and metabolism hormone receptors at once instead of one or two.

⏱ Half-life
~6 days (weekly dosing)
☉ Route
Subcutaneous injection
⚖ Evidence
Phase 3 ongoing
📚 Studies
4 referenced

It is currently investigational only, meaning it is not available as a prescription medicine anywhere in the world. The only legitimate way to receive it is by enrolling in a registered clinical trial. Anything sold online labelled 'retatrutide' is an unregulated research-chemical preparation with no quality guarantee.

02 How it works

The simple version, then the science.

Retatrutide mimics three of the body's own appetite and metabolism hormones at once. GLP-1 and GIP signalling reduce appetite and improve how the body handles sugar, similar to semaglutide and tirzepatide. The glucagon component is the new piece: it nudges the body to burn more energy and may help mobilise fat from the liver, on top of the appetite suppression.

Go deeper · the proposed mechanism

Retatrutide is a single peptide engineered to bind the GIP, GLP-1 and glucagon receptors with balanced agonist activity. The GLP-1 and GIP arms drive incretin-style effects, delayed gastric emptying, increased satiety, improved insulin secretion. The glucagon arm increases resting energy expenditure and hepatic lipid oxidation, which is thought to explain the additional weight loss and the early signal on liver fat reduction seen in phase 2. Pharmacokinetics support once-weekly subcutaneous dosing.

03 What it's used for

Each use graded by how strong the evidence actually is.

  • Moderate
    Obesity / weight loss🔬 Phase 2 trial (n=338) reported ~24% mean weight loss at 48 weeks on the 12 mg dose, the largest reduction reported for any obesity drug at that point. Phase 3 (TRIUMPH programme) is ongoing; results not yet read out.
  • Moderate
    Type 2 diabetes🔬 Phase 2 trial showed substantial reductions in HbA1c and body weight in adults with T2D. Phase 3 data still pending; not approved for diabetes.
  • Preclinical
    MASLD (fatty liver disease)🔬 Phase 2 substudy reported large reductions in liver fat. Promising mechanistic signal; trials in MASH are ongoing.
  • Anecdotal
    Online "research chemical" weight-loss use💬 Widely discussed in forums and sold by unregulated vendors. There is no quality control, no medical oversight, and no way to verify the contents.
Retatrutide is investigational. It is not approved as a medicine in the UK, US, EU or anywhere else. Every legitimate use is currently inside a clinical trial.

04 What the evidence says

The phase 2 obesity data, published in the New England Journal of Medicine in 2023, is genuinely striking: at the top 12 mg weekly dose, mean weight loss reached roughly 24% at 48 weeks, meaningfully above what has been seen with semaglutide or tirzepatide at the same time point. Phase 2 diabetes results in The Lancet are similarly strong on HbA1c and weight. Two caveats are important to hold simultaneously. First, phase 2 trials are smaller, shorter, and run in carefully selected populations; effect sizes routinely shrink at phase 3 and in broader real-world use. Second, there is no long-term safety record, the longest published data is around a year. Until the TRIUMPH phase 3 programme reads out and a regulator reviews it, the honest description is 'best preliminary obesity data we have ever seen, but unproven and unapproved'.

05 Dosing & administration

Reported in the literature, information not advice.

Trial protocols use once-weekly subcutaneous injection with a slow dose-titration over several months, starting at 2 mg/week and escalating to 4, 8 or 12 mg/week, to manage gastrointestinal side effects. These doses are for context only; there is no approved retatrutide product and no validated outpatient protocol. Any unsupervised use of compounded or grey-market 'retatrutide' is risky and outside the boundary of established medicine.

06 Side effects & safety

The safety profile from phase 2 looked broadly similar to other incretin drugs: mainly gastrointestinal, nausea, vomiting, diarrhoea, constipation, most often during dose escalation. The glucagon component introduces a theoretical risk of increased heart rate and changes in glucose handling that needs longer-term data to characterise properly. Because the published follow-up is short and the population studied is selective, rare or long-latency adverse events have not been ruled out. Pregnancy, breastfeeding, personal or family history of medullary thyroid cancer or MEN-2, severe gastrointestinal disease, and pancreatitis history are typical exclusions in trials of this class. Quality and content of any non-trial "retatrutide" is unknown and unverifiable.

Legal status: Investigational only. Not approved by FDA, MHRA or EMA. Legitimate access is via clinical trial enrolment only.

07 Where to buy (research use only)

Vetted on quality and transparency, not an endorsement to use.

ClinicalTrials.gov (TRIUMPH programme)
The only legitimate route to receive retatrutide today is enrolment in a registered phase 3 trial. Search "retatrutide" on ClinicalTrials.gov for currently recruiting sites.
Registered trialFree of chargeMedically supervised
View ↗
Online "research chemical" sellers
Any website selling "retatrutide" vials, peptide blends or compounded versions is selling an unregulated product. There is no approved retatrutide on the market, a finished prescription product does not exist yet. Contents, purity, sterility and dose accuracy cannot be verified.
Not recommendedUnregulatedQuality unverifiable
View ↗
Licensed UK / US pharmacies
No licensed pharmacy can supply retatrutide as a finished medicine because none exists. Anyone offering it via a 'telehealth clinic' or compounding service is operating outside the licensed supply chain.
Not availableNo approved product
View ↗
Disclosure: Pepwyse is not affiliated with these companies and does not earn any commission from these links; they are listed for reference only. These products are sold strictly for laboratory research use only and are not for human consumption.

09 Clinical studies & research

Primary sources. Read the science yourself.

Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial
New England Journal of Medicine (Jastreboff et al.) · 2023 Human · Phase 2 RCT
The headline obesity trial. 338 adults with BMI ≥30 (or ≥27 with comorbidities). Mean weight loss of ~24.2% at 48 weeks on 12 mg weekly versus ~2.1% on placebo. Gastrointestinal side effects were the most common adverse events. View on PubMed →
Retatrutide for Type 2 Diabetes, A Phase 2 Trial
The Lancet (Rosenstock et al.) · 2023 Human · Phase 2 RCT
Phase 2 study in 281 adults with type 2 diabetes. Reported substantial reductions in HbA1c and body weight across dose levels, with a side-effect profile similar to other incretin agonists. View on PubMed →
First-in-Human Pharmacology Study of LY3437943
Diabetes Care / Eli Lilly · 2022 Human · Phase 1
Single- and multiple-ascending-dose study in healthy adults and people with type 2 diabetes. Established pharmacokinetics supporting once-weekly dosing and an early signal on weight reduction. View on PubMed →
TRIUMPH Phase 3 Programme, Retatrutide in Obesity
ClinicalTrials.gov · 2024 Human · Phase 3 ongoing
The pivotal phase 3 obesity programme. Multiple registered trials covering obesity with and without comorbidities, including cardiovascular outcomes. Results pending; these are the readouts that will determine approvability. View on ClinicalTrials.gov →

10 Frequently asked questions

Is retatrutide approved?
No. Retatrutide is not approved as a medicine in the UK, US, EU or anywhere else. It is currently in phase 3 clinical trials. The earliest plausible approval is some time after those trials report and a regulator reviews the data.
How does retatrutide compare to semaglutide and tirzepatide?
In phase 2, retatrutide produced roughly 24% mean weight loss at 48 weeks on its top dose, larger than the phase 3 results reported for semaglutide (~15%) or tirzepatide (~20–22%) at similar time points. Direct head-to-head trials have not been run, and phase 2 effects often shrink when tested in larger, broader populations at phase 3.
Can I buy retatrutide online?
You can find websites selling vials labelled "retatrutide", but they are not selling an approved medicine, no approved retatrutide product exists yet. These are unregulated research-chemical preparations with no verified purity, dose accuracy or sterility. The only legitimate route to receive retatrutide is enrolment in a registered clinical trial.
Is retatrutide banned in sport?
Retatrutide is not named on the WADA Prohibited List, but as an unapproved investigational compound it is captured by category S0 ("Non-Approved Substances"), which prohibits any pharmacological substance not currently approved by a governmental regulatory authority. In tested sport, treat it as banned at all times.
How can I take part in a retatrutide trial?
Search "retatrutide" on ClinicalTrials.gov for currently recruiting sites in the TRIUMPH programme. Trials have strict eligibility criteria (BMI, comorbidities, medication history) and a screening process; participation is free and medically supervised.
Peppy
AI · knows this page
Hi, I'm Peppy, an AI assistant. Ask me anything about Retatrutide or any peptide.
How does it compare to semaglutide?When could it be approved?Is it safe?
Peppy is an AI, not a doctor. Information only, every question is logged to improve our content.