An investigational peptide drug from Eli Lilly that activates three hormone receptors at once: GIP, GLP-1 and glucagon. It is not an approved medicine.

What did the first big trial show?

A Phase 2 trial in 338 adults with obesity, published in the New England Journal of Medicine in 2023, found large average weight reductions over 48 weeks compared with placebo. Stomach and gut side effects were the most common.

Several Phase 3 trials have now been published, including TRIUMPH-1 (NEJM, 2026), TRIUMPH-2 (Lancet, 2026) and TRANSCEND-T2D-1 (Lancet, 2026). Others, including a long cardiovascular and kidney outcomes trial, are still running.

Is retatrutide approved?

No. The most recent trial papers we reviewed, from October 2026, still describe it as investigational.

Is the "retatrutide" sold online the same thing?

Not necessarily. Trial drug is made by the developer under drug manufacturing rules. Products sold online as research chemicals are not, and their contents are unverified.

Research guide

Retatrutide: What the Research Shows So Far

Quick answers

What is retatrutide?: An investigational peptide drug from Eli Lilly that activates three hormone receptors at once: GIP, GLP-1 and glucagon. It is not an approved medicine.
What did the first big trial show?: A Phase 2 trial in 338 adults with obesity, published in the New England Journal of Medicine in 2023, found large average weight reductions over 48 weeks compared with placebo. Stomach and gut side effects were the most common.
Where is Phase 3?: Several Phase 3 trials have now been published, including TRIUMPH-1 (NEJM, 2026), TRIUMPH-2 (Lancet, 2026) and TRANSCEND-T2D-1 (Lancet, 2026). Others, including a long cardiovascular and kidney outcomes trial, are still running.
Is retatrutide approved?: No. The most recent trial papers we reviewed, from October 2026, still describe it as investigational.
Is the "retatrutide" sold online the same thing?: Not necessarily. Trial drug is made by the developer under drug manufacturing rules. Products sold online as research chemicals are not, and their contents are unverified.

Retatrutide has drawn more attention than almost any drug still in development. The reason is simple: its trial results for weight reduction have been larger than those of earlier drugs in the same family. This page summarizes what the published research actually shows, what is still unknown, and why it remains an investigational drug.

This is a research summary. It is not medical advice and it does not discuss personal use. Products sold online as "research" retatrutide are for research use only and are not for human consumption.

How it works, in brief

Retatrutide is a single peptide built to activate three receptors:

GLP-1 receptor, the target of semaglutide. It affects appetite and insulin release.
GIP receptor, which together with GLP-1 is the target of tirzepatide.
Glucagon receptor, which researchers think may add an effect on energy use and liver fat.

That three-way action is why it is often called a "triple agonist." For background on what an agonist is, see What Is a Receptor Agonist?

The Phase 2 obesity trial (NEJM, 2023)

The first major result came from a Phase 2 trial led by Jastreboff and colleagues and published in the New England Journal of Medicine in 2023. It was double-blind, randomized and placebo-controlled, and was funded by Eli Lilly.

Who: 338 adults with obesity, or with overweight plus at least one weight-related condition.
Design: several retatrutide dose groups compared with placebo, once weekly for 48 weeks.
Main result: at 48 weeks, average body-weight change ranged from about 8.7% lower in the lowest dose group to 24.2% lower in the highest, compared with 2.1% lower on placebo.
Side effects: mostly gastrointestinal, related to dose, and mostly mild to moderate. Heart rate rose in a dose-related way, peaked at 24 weeks, then declined.

A companion Phase 2 trial in people with type 2 diabetes was published in The Lancet the same year.

Phase 3: the TRIUMPH and TRANSCEND programs

Phase 3 trials are the large studies regulators rely on. For what the phases mean, see Phase 1, 2, 3: What Trial Phases Mean. Several retatrutide Phase 3 trials have now reported in peer-reviewed journals.

TRIUMPH-1 (NEJM, 2026)

This trial enrolled 2,339 adults with obesity but without diabetes, for 80 weeks. Average weight change was about 25.0% lower in the highest dose group, compared with 3.9% lower on placebo. The trial also included subgroups with knee osteoarthritis, where pain scores improved more than with placebo, and with obstructive sleep apnea, where breathing events during sleep fell more than with placebo. The most common adverse events were gastrointestinal.

TRIUMPH-2 (Lancet, 2026)

This trial enrolled 1,152 adults with obesity or overweight and type 2 diabetes, for 80 weeks. Average weight change was about 18.8% lower in the highest dose group, compared with 5.1% lower on placebo. Diarrhea and nausea were more common with retatrutide. Low blood pressure and dysesthesia, an abnormal skin sensation, were also reported more often than with placebo. Stopping treatment because of adverse events was more common in the two higher dose groups than on placebo.

TRANSCEND-T2D-1 (Lancet, 2026)

This 40-week trial in 537 adults with type 2 diabetes tested retatrutide on its own. HbA1c, a measure of long-term blood sugar, fell more with every retatrutide dose than with placebo.

Still running

Registry records on ClinicalTrials.gov list other Phase 3 trials still active. They include a head-to-head trial against tirzepatide and a large cardiovascular and kidney outcomes trial with an estimated primary completion in 2029. That outcomes trial is the kind of study that answers long-term safety questions.

What we don't know yet

Long-term safety. The longest published trials run about 80 weeks. Effects on heart and kidney events are still being studied.
How it compares head to head with tirzepatide and semaglutide in the same trial. Comparing numbers across separate trials is unreliable. See what head-to-head trials show for why.
What happens after stopping. A weight-maintenance trial is still running.
The heart rate signal seen in Phase 2, and what it means over years.

Also note who ran the research. These trials were funded by Eli Lilly, the developer. That is normal for drug development, and the results went through peer review. It is still worth knowing. See Who Funded the Study?

Investigational means not approved

Retatrutide has not been approved as a medicine. The trial results above apply to drug made by the developer, used inside controlled trials with medical monitoring. They do not apply to anything else sold under the same name.

That matters because products labeled retatrutide are sold online as research chemicals. In 2026, a case report described a man with type 1 diabetes who became seriously ill after using an online-purchased product marketed as retatrutide. The authors could not establish cause, since an infection was also present. They noted that the composition, purity and dosing accuracy of such products are uncertain. One case proves little by itself, but it shows the gap between a trial drug and an unverified vial.

Registry records can mislead too. Our page on what "research use only" means documents a template ClinicalTrials.gov record that copied the identity of a real retatrutide study.

For the Evidence Index entry, see Retatrutide. For the label on research-market products, see What Are Research Peptides?

Sources

Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial. N Engl J Med. 2023;389(6):514-526. PubMed 37366315 · DOI
Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial conducted in the USA. Lancet. 2023. PubMed 37385280 · DOI
Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1). N Engl J Med. 2026. PubMed 42814954 · DOI
Bellido V, le Roux CW, Ekinci EI, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a phase 3 trial. Lancet. 2026;408(10563):1455-1472. PubMed 42810372 · DOI
Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a phase 3 trial. Lancet. 2026;407(10546):2402-2413. PubMed 42250575 · DOI
Grunstein RR, Somers VK, Azarbarzin A, et al. Retatrutide once weekly for treatment of obstructive sleep apnea. N Engl J Med. 2026. PubMed 42904878 · DOI
Branine N. Online-sourced retatrutide complicating impending diabetic ketoacidosis in a patient with type 1 diabetes and concurrent Shigella gastroenteritis. Cureus. 2026;18(8):e115260. PubMed 42669023 · DOI
ClinicalTrials.gov. TRIUMPH-1 master protocol, NCT05929066. Source
ClinicalTrials.gov. Retatrutide cardiovascular and kidney outcomes trial, NCT06383390. Source
ClinicalTrials.gov. Retatrutide compared to tirzepatide in adults with obesity, NCT06662383. Source

Peptide Proof reports what studies found. Research peptides are for research use only and are not for human consumption. Nothing on this page is medical advice, dosing guidance or a treatment recommendation.