Retatrutide

What it is

Retatrutide, also known by its code name LY3437943, is a single peptide developed by Eli Lilly that activates three receptors: those for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon [1]. It is given as a once-weekly subcutaneous injection in clinical trials [3]. It is an investigational molecule, which means it has not been approved by FDA or any other regulator, there is no prescribing label, and Lilly states it is legally available only to participants in its clinical trials [3]. FDA says retatrutide is not a component of any approved drug, has not been found safe and effective for any condition, and cannot be used in compounding under federal law [5]. STACK includes it because people ask about it; the page is education, not a recommendation.

How it works

The three target receptors each have a role in energy balance. GLP-1 and GIP are gut hormones released after meals; glucagon is a pancreatic hormone. Retatrutide is described by its developers as a triple hormone receptor agonist that activates all three [4]. In the phase 1b study in people with type 2 diabetes, 12 weeks of once-weekly injections lowered daily plasma glucose and glycated hemoglobin in the higher-dose groups and produced dose-dependent weight reduction [1]. The phase 2 obesity trial also observed dose-dependent increases in heart rate that peaked at 24 weeks and declined afterwards [2]. How much each receptor contributes to the overall effect in humans has not been published in the sources fetched for this page, so this section stays with what the trials report.

What the evidence shows

The phase 2 trial (NEJM 2023) enrolled 338 adults with obesity, or overweight plus a weight-related condition, for 48 weeks. Weight change at 48 weeks ranged from -8.7% in the lowest group to -24.2% in the highest, versus -2.1% on placebo [2]. In the phase 3 TRIUMPH-1 trial, announced May 21 2026, adults with obesity or overweight and no diabetes lost an average of 19.0%, 25.9% and 28.3% of body weight at 80 weeks across the three studied doses, versus 2.2% on placebo [3]. On Jul 23 2026 Lilly reported TRIUMPH-2, in adults with type 2 diabetes and obesity or overweight, with up to 20.8% average weight loss at 80 weeks, and TRIUMPH-3, in adults with severe obesity and established cardiovascular disease, with up to 22.6% [4]. These are sponsor topline announcements; full peer-reviewed results have not yet been published [4].

Regulatory status

Retatrutide is not an FDA-approved drug as of Sep 24 2026. It is in phase 3 development in Lilly’s TRIUMPH program, which began in 2023 and has enrolled more than 5,800 participants across obesity, obstructive sleep apnea and knee osteoarthritis trials [4]. On Jul 23 2026 Lilly said it is completing the manufacturing data package for a Biologics License Application and plans to submit retatrutide to FDA for US approval in Q1 2027 [4]. Lilly states the molecule cannot be legally sold or marketed for human use [4]. FDA’s page on unapproved GLP-1 drugs, current as of Sep 1 2026, says retatrutide cannot be used in compounding under federal law and that FDA has warned telehealth companies, ingredient distributors and outsourcing facilities over marketing, selling or repackaging it, including products falsely labelled “for research purposes” [5].

Half-life and what it means for a level curve

The only published human value comes from the phase 1b trial in the Lancet: in 72 adults with type 2 diabetes receiving once-weekly subcutaneous injections for 12 weeks, pharmacokinetics were dose proportional and the half-life was approximately 6 days [1]. The reference half-life in STACK is 144 hours. Confidence is medium: it is a single early-phase study, the value is stated as approximate, and no regulatory label has confirmed it. With a 6-day half-life and weekly injections, roughly 45% of a dose remains when the next one is given, so the curve shows a modest weekly sawtooth that climbs toward a plateau. With regular dosing a level reaches about 97% of steady state after about 5 half-lives, here roughly 30 days. STACK’s curve is an estimate from this published half-life, not a blood level. If a later label reports a different value, STACK will update the reference.

Reported side effects

There is no FDA label, so the only human safety data come from trials. In the phase 1b study, treatment-emergent adverse events were reported by 63% of participants on retatrutide, and gastrointestinal disorders were the most frequent [1]. In the phase 2 trial, the most common adverse events were gastrointestinal, dose-related and mostly mild to moderate, and heart rate increased in a dose-dependent way before declining after week 24 [2]. In TRIUMPH-1, nausea was reported by 28.6 to 42.4% across the three doses versus 14.8% on placebo, diarrhea by 25.2 to 34.1% versus 13.5%, constipation by 23.8 to 26.1% versus 10.9%, vomiting by 10.6 to 25.3% versus 4.8%, and dysesthesia (abnormal skin sensation) by 5.1 to 12.5% versus 0.9%; discontinuation for adverse events ranged from 4.1 to 11.3% versus 4.9% [3]. TRIUMPH-2 and TRIUMPH-3 reported a similar pattern, with discontinuation for adverse events up to 13.5% [4]. Anyone using a product labelled retatrutide should discuss any symptom with their prescriber.

Storage and handling

Because retatrutide has no approved label, there are no official storage instructions. Lilly states the molecule is legally available only to participants in its clinical trials, where the study site handles supply and storage [3]. FDA says retatrutide cannot be used in compounding and is not a component of any approved drug, so no pharmacy label should exist for it either [5]. FDA’s general guidance for injectable GLP-1 drugs is that they require refrigeration as described in their package inserts, that a product arriving warm or without adequate cooling should not be used, and that a vial containing multiple doses should be discarded 28 days after first use with a new sterile needle and syringe for each dose [5]. If a prescriber has given you a product labelled retatrutide, the dispensing label governs, and STACK’s reconstitution calculator does the volume arithmetic only; it does not suggest amounts.

What STACK tracks for it

If your prescriber has written retatrutide into your plan, STACK logs each dose exactly as written, in milligrams, with the date and time. It draws an estimated level curve from the 144-hour reference half-life and flags that the value is medium-confidence and from a phase 1b study [1]. You can enter your own half-life estimate if you and your prescriber prefer. It stores whatever escalation schedule your prescriber gave you so you can see where you are on it, without proposing one. Injection sites, weight, heart rate if you choose to log it, side effects such as nausea or skin sensation changes and how long they lasted, and vial inventory with a 28-day open-vial countdown are tracked alongside [5]. STACK shows your data; it never prescribes, and it is not a source for the compound.

The reference half-life in STACK

STACK's simulator and the app use 144 h (6 days) for Retatrutide: approximately 6 days (about 144 h); one published phase 1b value, no FDA label. Measured in: adults with type 2 diabetes in a 12-week phase 1b multiple-ascending-dose study, subcutaneous once weekly.

Estimate only. Modelled from the published half-life you selected and the doses you logged — not a measured blood level. Do not use it to make medication decisions.

Free tools for Retatrutide

Read next

Sources

Every URL below was fetched and checked on 2026-09-24. Bracketed numbers in the text link here.

1. TrialLY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b trial, Lancet 2022
2. TrialTriple-Hormone-Receptor Agonist Retatrutide for Obesity, a Phase 2 Trial, N Engl J Med 2023
3. OtherLilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1), May 21 2026
4. OtherLilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3), Jul 23 2026
5. FDAFDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss (current as of Sep 1 2026)