An investigational synthetic peptide that acts at three receptors at once — GIP, GLP-1 and glucagon. It adds glucagon receptor agonism, which raises energy expenditure, to the dual incretin activity of tirzepatide.

Is retatrutide approved anywhere?

No. It holds no marketing authorisation in any jurisdiction, no regulator has completed an assessment, and there is no approved product information for it. It is supplied here as laboratory reagent for in-vitro research only.

What did the retatrutide trial find?

In a randomised, double-blind, placebo-controlled phase 2 trial in 338 adults with obesity, mean body weight change at 48 weeks ranged from −8.7% to −24.2% across treatment groups against −2.1% on placebo. That is the whole published human evidence base for the compound.

What adverse findings were reported?

The trial reported dose-dependent increases in heart rate that peaked at 24 weeks and declined afterwards, with gastrointestinal events the most frequently reported class. A phase 2 trial is not designed to establish safety, so these identify what to watch rather than settling anything.

How does retatrutide compare with tirzepatide or semaglutide?

No head-to-head trial has been published, so any comparison is between separate trials with different populations, durations and designs. That is a weak basis for ranking compounds, and the difference in evidence maturity — one phase 2 trial against completed phase 3 programmes — matters more than the headline percentages.

Research guides

Retatrutide (LY3437943): what the research says

A triple hormone receptor agonist still in development, with no marketing authorisation anywhere. What the published phase 2 work reported, and what it did not.

Available in the catalogue

Supplied as research material. Sizes and pricing are on the product page. Availability is not a statement about what a compound does.

RETATRUTIDE
Metabolic & GLP-1

Retatrutide is the newest of the three incretin compounds in this catalogue and the one with the thinnest evidence base — a single published phase 2 trial. It is also the one whose regulatory position is simplest to state, and the simplicity cuts the other way from semaglutide and tirzepatide.

Authorised nowhere

Semaglutide and tirzepatide are the active ingredients of authorised medicines, and the caution there is that a research vial is not that product. Retatrutide is investigational. It holds no marketing authorisation in any jurisdiction, no regulator has completed an assessment of it, and there is no approved product information setting out what is known about its safety.

That means there is no pharmaceutical-grade comparator to distinguish a research vial from, and it also means nobody has yet done the work that turns a phase 2 signal into an established profile. Both facts follow from the same thing: development is not finished.

What the molecule is

A synthetic peptide agonist at three receptors at once — GIP, GLP-1 and glucagon — also designated LY3437943. It extends the incretin approach by adding glucagon receptor agonism to the dual activity of tirzepatide. Glucagon receptor activation raises energy expenditure, which is a different lever from the appetite and insulin effects of the other two, and that combination is the stated rationale for the molecule.

One trial, and what it measured

Jastreboff and colleagues enrolled 338 adults with obesity in a randomised, double-blind, placebo-controlled phase 2 trial and followed body weight to 48 weeks across four treatment groups. Mean change at 48 weeks ranged from −8.7% in the lowest group to −24.2% in the highest, against −2.1% on placebo. At 48 weeks, weight reduction of 5% or more, 10% or more and 15% or more had occurred in 92%, 75% and 60% of the 4 mg group, rising to 100%, 93% and 83% in the 12 mg group, against 27%, 9% and 2% on placebo.

The same trial reported dose-dependent increases in heart rate, peaking at 24 weeks and declining thereafter. That is a finding from the trial and not a footnote to it, and it is listed below alongside the efficacy result.

A phase 2 trial is designed to find out whether a compound is worth studying further, and to identify what to watch. It is not designed to establish safety, and its results are the beginning of an evidence base rather than a conclusion about one.

What studies reported

Each entry states what a study examined and the model it used. Nothing below describes an outcome for a person.

Everything below is drawn from published research, and each entry names the model the study used. Approval status varies by compound and by country, and nothing described here is supplied as a medicine or for use in a person.

Jastreboff et al. (2023)New England Journal of Medicine · 389(6):514–26
Reported mean body weight change at 48 weeks ranging from −8.7% to −24.2% across treatment groups against −2.1% on placebo, in adults with obesity. Weight reduction of 5% or more, 10% or more and 15% or more occurred in 92%, 75% and 60% of the 4 mg group and 100%, 93% and 83% of the 12 mg group, against 27%, 9% and 2% on placebo.
human, randomised double-blind placebo-controlled phase 2, 338 adults Source

Adverse and null findings reported

Harms, tolerability observations, and trials that did not meet their endpoint. A negative result is a finding and is listed here rather than omitted.

Jastreboff et al. (2023)New England Journal of Medicine · 389(6):514–26
The same trial reported dose-dependent increases in heart rate that peaked at 24 weeks and declined thereafter, alongside gastrointestinal adverse events that were the most frequently reported class of event.
human, randomised double-blind placebo-controlled phase 2, 338 adults Source

What the research does not establish

An absence cannot be cited, so these are stated plainly. They are the part of the picture that silence would otherwise hide.

No phase 3 result has been published. The entire published human evidence base for this compound is one phase 2 trial in 338 adults over 48 weeks.
The compound holds no marketing authorisation in any jurisdiction and no regulator has completed an assessment of it. There is no approved product information stating what is known about its safety.
No withdrawal trial has been published. The comparable trials for semaglutide and tirzepatide both found that a large share of the effect reverses within a year of stopping, and whether that holds here has not been tested.
The heart rate finding was observed over 48 weeks and was declining at the end of the observation period. What it does over longer durations is unknown.
Because the compound is authorised nowhere, there is no pharmaceutical-grade reference product against which research-grade material could be characterised.

Common questions

What is retatrutide?: An investigational synthetic peptide that acts at three receptors at once — GIP, GLP-1 and glucagon. It adds glucagon receptor agonism, which raises energy expenditure, to the dual incretin activity of tirzepatide.
Is retatrutide approved anywhere?: No. It holds no marketing authorisation in any jurisdiction, no regulator has completed an assessment, and there is no approved product information for it. It is supplied here as laboratory reagent for in-vitro research only.
What did the retatrutide trial find?: In a randomised, double-blind, placebo-controlled phase 2 trial in 338 adults with obesity, mean body weight change at 48 weeks ranged from −8.7% to −24.2% across treatment groups against −2.1% on placebo. That is the whole published human evidence base for the compound.
What adverse findings were reported?: The trial reported dose-dependent increases in heart rate that peaked at 24 weeks and declined afterwards, with gastrointestinal events the most frequently reported class. A phase 2 trial is not designed to establish safety, so these identify what to watch rather than settling anything.
How does retatrutide compare with tirzepatide or semaglutide?: No head-to-head trial has been published, so any comparison is between separate trials with different populations, durations and designs. That is a weak basis for ranking compounds, and the difference in evidence maturity — one phase 2 trial against completed phase 3 programmes — matters more than the headline percentages.

Compounds covered

The reference page for each compound this article discusses.

Retatrutide

Tirzepatide: what the research says
A dual GIP and GLP-1 receptor agonist, and the active ingredient of EU-authorised medicines. What the trials reported, and what no trial has studied.
Semaglutide: what the research says
A GLP-1 receptor agonist and the active ingredient of EU-authorised medicines. What the trials reported, the discontinuation rates, and the open questions.
How to store research peptides
Lyophilised peptides at -20°C, reconstituted at 2–8°C, ambient in transit. Why the dry cake tolerates shipping, and what actually degrades a vial.

About this article

Everything reported here comes from published research, and each finding names the model the study used — cell culture, rat, or human. Findings in one model do not transfer to another, most of the work described is preclinical, and none of it is a claim that a compound is safe or effective for any purpose. Nothing on this page describes doses, routes of administration, or use in a person.

Approval status varies by compound and by country. A few of the substances described are the active ingredient of medicines authorised in the EU; most have no marketing authorisation anywhere and have never been assessed by a regulator. Neither is supplied as a medicine here. All material supplied by ASSAY is sold for in-vitro laboratory research only, and is not a drug, food, cosmetic or medical device, and not for human or veterinary use.

All guides