Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
A 39-residue GIP-based peptide with three non-canonical residues and a C20 fatty diacid — the first triple-agonist to reach phase 3.
Also known as: LY3437943 · GGG tri-agonist · triple agonist · “GLP-3” (informal, inaccurate)
Part of the Metabolic & GLP-1 peptides cluster
Retatrutide — evidence brief
The phase 3 reports measured weight change with and without type 2 diabetes, or HbA1c change on diet and exercise alone. The liver report reused a subset of an earlier obesity trial. Different populations, endpoints and estimands prevent a ranking across these trials; imaging liver-fat reduction does not establish clinical liver outcomes.
- Version
- 2026-10-05.1
- Snapshot updated
Prepared by Peptides Codex. Independent review by a qualified subject specialist is pending.
Scope of this brief
Four selected primary reports identified through October 5, 2026, on study-supplied subcutaneous retatrutide (LY3437943), funded by Eli Lilly. Arm doses describe study conditions, not instructions or authentication of research powders. This is not an exhaustive review; qualified scientific review remains pending.
Jastreboff et al., 2026 · TRIUMPH-1 · PMID 42814954
- Material tested
- Study-supplied subcutaneous retatrutide (LY3437943), target arms 4/9/12 mg versus placebo.
- Model or population
- Adults without diabetes: BMI ≥30, or ≥27 with a weight-related complication.
- Study design
- TRIUMPH-1: phase 3, randomized, double-blind; 80 weeks. Primary weight comparisons: 9/12 mg versus placebo; additional subgroup pain and sleep-apnea endpoints.
- Sample and comparison
- Paper reports 2,339 randomized; official registry lists 2,335 enrolled. Difference unresolved; arm-level analysis counts not verified in the retrieved abstract.
- Reported finding
- Week-80 weight change, treatment-regimen/ITT estimate: −17.6/−23.7/−25.0% for 4/9/12 mg versus −3.9% placebo. Primary 9/12-mg differences: −19.8/−21.0 percentage points (both p<0.001).
- Limits of this evidence
- Pain and sleep-apnea primary results concern subgroups and different estimands, not the full weight population. Gastrointestinal events were most common; detailed methods and longer-term safety are not established by this abstract.
Source access: Primary journal and PubMed abstracts plus official registry inspected; full text and supplement could not be retrieved. Enrollment discrepancy remains unresolved.
Primary source ↗: Jastreboff et al., 2026 · TRIUMPH-1 · PMID 42814954
Bellido et al., 2026 · TRIUMPH-2 · PMID 42810372
- Material tested
- Study-supplied subcutaneous retatrutide (LY3437943), target arms 4/9/12 mg versus placebo.
- Model or population
- Adults with BMI ≥27 and type 2 diabetes, HbA1c 6.5–10.5%, on stable diet/exercise alone or up to three oral glucose-lowering medicines.
- Study design
- TRIUMPH-2: phase 3, randomized 1:1:1:1, double-blind, placebo-controlled; 80 weeks. Primary weight comparisons: 9/12 mg; 4 mg was a key secondary comparison.
- Sample and comparison
- 1,152 randomized/analyzed: 292/284/287 versus 289; 965 completed study drug. Safety counts: 292/284/286 versus 287 who received drug. Primary missing values multiply imputed.
- Reported finding
- Primary week-80 weight change, treatment-regimen estimate: −16.8/−18.8% for 9/12 mg versus −5.1% placebo. Differences: −11.8/−13.8 percentage points (95% CI −13.7 to −9.8/−15.8 to −11.8; both p<0.0001).
- Limits of this evidence
- Placebo comparison in a selected diabetes population. Gastrointestinal events were more frequent with retatrutide; permanent discontinuation due to adverse events or death was 12/8% at 9/12 mg versus 5% placebo. No active-drug ranking or long-term safety conclusion.
Source access: Primary PubMed abstract and official registry inspected; publisher full text could not be retrieved. Analysis populations and imputation are stated in the abstract; detailed methods were not read.
Primary source ↗: Bellido et al., 2026 · TRIUMPH-2 · PMID 42810372
Bajaj et al., 2026 · TRANSCEND-T2D-1 · PMID 42250575
- Material tested
- Study-supplied subcutaneous retatrutide (LY3437943), target arms 4/9/12 mg versus placebo.
- Model or population
- Adults with type 2 diabetes inadequately controlled by diet/exercise alone, HbA1c 7.0–9.5% and BMI ≥23.
- Study design
- TRANSCEND-T2D-1: phase 3, randomized 1:1:1:1, double-blind, placebo-controlled; 40 weeks. Primary endpoint: HbA1c change.
- Sample and comparison
- 537 randomized: 134/133/136 versus 134 placebo. 490 completed the treatment period on drug; 504 completed the study. Abstract does not detail analysis-set exclusions.
- Reported finding
- Primary week-40 HbA1c change, treatment-regimen estimate: −1.69/−1.86/−1.94 percentage points for 4/9/12 mg versus −0.81 placebo. Adjusted differences: −0.88/−1.04/−1.12 points (all p<0.0001); not relative percent changes.
- Limits of this evidence
- Monotherapy population and 40-week glycemic endpoint; not a cardiovascular-outcomes trial. Gastrointestinal events were common; adverse-event discontinuations were 2–5% versus 0% placebo. Full estimand implementation and long-term safety remain unverified here.
Source access: Primary PubMed abstract and official registry inspected; publisher full text could not be retrieved. Detailed missing-data methods and analysis-set counts were not available in the abstract.
Primary source ↗: Bajaj et al., 2026 · TRANSCEND-T2D-1 · PMID 42250575
Sanyal et al., 2024 · MASLD substudy · PMID 38858523
- Material tested
- Study-supplied subcutaneous retatrutide (LY3437943), 1/4/8/12 mg versus matching placebo, with lifestyle counseling. Starting-dose subgroups pooled at 4/8 mg.
- Model or population
- Adults without diabetes in an obesity trial, with baseline MRI liver fat ≥10%; selected MASLD substudy.
- Study design
- Phase 2a substudy of randomized, double-blind NCT04881760; 48-week treatment, primary liver-fat endpoint at 24 weeks. Efficacy estimand excludes post-discontinuation data; continuous-outcome mixed model without imputation.
- Sample and comparison
- 98 of the parent trial's 338 participants: 20/19/22/18 versus 19 placebo. Week-24 MRIs available for 77: 16/15/17/15 versus 14. Shared cohort, not independent replication.
- Reported finding
- Primary relative MRI-PDFF liver-fat change at week 24: −42.9/−57.0/−81.4/−82.4% for 1/4/8/12 mg versus +0.3% placebo (all p<0.001). These are relative reductions, not absolute liver-fat percentage-point changes.
- Limits of this evidence
- Small selected subset, missing imaging and exclusion of data after intercurrent events; no multiplicity adjustment. Imaging fat reduction does not demonstrate biopsy-confirmed MASH resolution, fibrosis regression or clinical liver benefit. Sponsor participated in design, analysis and report writing.
Source access: Primary Nature Medicine full text inspected, including Methods, Results, figure counts and limitations; parent registry corroborated. Supplementary files and individual participant data not reviewed.
Primary source ↗: Sanyal et al., 2024 · MASLD substudy · PMID 38858523
A finding applies to the material, model and conditions studied. It does not establish safety or effectiveness in other settings.
Overview
Retatrutide (LY3437943) is an investigational 39-amino-acid peptide (C221H342N46O68, ≈4,731 Da) that activates three receptors — GIP, GLP-1 and glucagon. It shares its GIP-based scaffold and exendin-4 tail with tirzepatide, adds α-methyl-leucine and a second Aib, and carries a C20 fatty diacid on Lys17 for a half-life of about 6 days. In phase 2 it produced a mean weight change of −24.2% at 48 weeks; phase 3 trials are ongoing and it is not yet approved.
Source & context
Biological / chemical source: Synthetic engineered peptide
Primary research or clinical context: Investigational — phase 3 trials in obesity, type 2 diabetes, MASLD, sleep apnoea and cardiovascular outcomes; not approved anywhere as of September 2026
What retatrutide is
Retatrutide (Eli Lilly code LY3437943) is a single synthetic peptide of 39 amino acids designed to activate three metabolic hormone receptors at once: the GIP receptor, the GLP-1 receptor and the glucagon receptor. It is often called a “triple agonist” or “GGG tri-agonist”. Structurally it is a close sibling of tirzepatide — same length, same GIP-based scaffold, same exendin-4-derived tail, same C20 fatty diacid — with a handful of substitutions that switch on glucagon receptor activity. Its molecular formula is C221H342N46O68 and its average molecular weight is about 4,731 Da. As of September 2026 it is investigational: phase 3 trials are under way and it is not approved for sale anywhere.
Why “GLP-3” is a misnomer
Search results and forums often call retatrutide “GLP-3”, as if it were a third-generation hormone after GLP-1 and GLP-2. There is no such hormone, and GLP-2 (a real gut peptide) has nothing to do with it. The nickname is shorthand for “three receptors”, and retatrutide does not even come from the GLP-1 sequence — like tirzepatide, its backbone is GIP-derived. The accurate description is a GIP/GLP-1/glucagon receptor triple agonist. Knowing this helps when reading the literature, where the term GLP-3 never appears.
Sequence, modifications and how it differs from tirzepatide
In one-letter code with the modifications spelled out: Y-[Aib]-Q-G-T-F-T-S-D-Y-S-I-[αMeLeu]-L-D-K-K(C20 diacid-γGlu-OEG)-A-Q-[Aib]-A-F-I-E-Y-L-L-E-G-G-P-S-S-G-A-P-P-P-S-NH2. Three residues are non-canonical, shown as X in the chip display above: Aib at positions 2 and 20 and α-methyl-L-leucine at position 13. The fatty diacid is attached to lysine 17 through a γ-glutamate and a single OEG spacer — tirzepatide, by contrast, acylates lysine 20 through two OEG units. The middle of the chain (positions 3, 13, 16–28) is where the two peptides diverge: retatrutide's substitutions there are what give it glucagon receptor activity. The assignments follow PubChem's deposited structure (CID 171390338) and the IUPHAR Guide to Pharmacology.
| Feature | Tirzepatide | Retatrutide |
|---|---|---|
| Length | 39 aa | 39 aa |
| Scaffold | GIP core + exendin-4 tail | GIP core + exendin-4 tail |
| Non-canonical residues | Aib2, Aib13 | Aib2, αMeLeu13, Aib20 |
| Acylation site | Lys20 | Lys17 |
| Lipid | C20 diacid-γGlu-2×OEG | C20 diacid-γGlu-OEG |
| Receptors | GIP + GLP-1 | GIP + GLP-1 + glucagon |
| Formula / mass | C225H348N48O68 / ≈ 4,814 Da | C221H342N46O68 / ≈ 4,731 Da |
| Half-life | ≈ 5 days | ≈ 6 days |
Mechanism of action: what each receptor contributes
GLP-1 receptor activation reduces appetite, slows gastric emptying and amplifies glucose-dependent insulin secretion — the foundation shared with semaglutide. GIP receptor activation adds insulin secretion and effects in adipose tissue and the brain, and appears to soften GLP-1-related nausea; this is tirzepatide's advantage. The glucagon receptor is the new element. Glucagon raises energy expenditure and drives fat oxidation in the liver, which is why retatrutide produced unusually large reductions in liver fat in its MASLD substudy — but glucagon also raises blood glucose, so its activity has to be balanced against the two incretin receptors. Retatrutide's designers set the ratio so the molecule is GIPR-favouring, with lower glucagon receptor potency, and the phase 2 diabetes trial confirmed glucose fell rather than rose.
Half-life and dosing cadence in trials
Phase 1 pharmacokinetics were dose-proportional with a mean half-life of about 6 days, which supports once-weekly subcutaneous injection — the schedule used in every trial since. Because gastrointestinal side effects scale with dose, the trials escalated: the phase 2 obesity study started participants at 2 mg or 4 mg weekly and stepped up over several weeks to maintenance doses of 4, 8 or 12 mg, and the lower 2 mg start reduced early nausea and vomiting. The phase 3 TRANSCEND-T2D-1 trial used 4, 9 and 12 mg maintenance doses. The dosing guide linked below lists the exact arms used in each published trial; it is a description of protocols, not a recommendation.
Clinical evidence: phase 2 in obesity and type 2 diabetes
The phase 2 obesity trial (Jastreboff et al., NEJM 2023; 338 adults, 48 weeks) is the study behind most retatrutide headlines. At 24 weeks the mean weight change was −7.2% (1 mg), −12.9% (4 mg), −17.3% (8 mg) and −17.5% (12 mg) versus −1.6% with placebo. At 48 weeks it was −8.7%, −17.1%, −22.8% and −24.2% versus −2.1% — and 83% of the 12 mg group had lost at least 15% of body weight. Weight was still falling at 48 weeks, so the plateau was not reached. The parallel phase 2 trial in type 2 diabetes (Rosenstock et al., Lancet 2023) showed HbA1c reductions of up to about 2 percentage points and weight loss of about 17% at 36 weeks on 12 mg, with dulaglutide 1.5 mg as an active comparator.
| Arm | 24 weeks | 48 weeks | ≥15% loss at 48 wk |
|---|---|---|---|
| Placebo | −1.6% | −2.1% | 2% |
| 1 mg | −7.2% | −8.7% | — |
| 4 mg | −12.9% | −17.1% | 60% |
| 8 mg | −17.3% | −22.8% | 75% |
| 12 mg | −17.5% | −24.2% | 83% |
Phase 3 (TRIUMPH, TRANSCEND) and approval status
Lilly's phase 3 programme runs under two names: TRIUMPH (obesity and its complications, including knee osteoarthritis, sleep apnoea and cardiovascular outcomes) and TRANSCEND (type 2 diabetes). The first full phase 3 publication, TRANSCEND-T2D-1 (Bajaj et al., Lancet, June 2026), randomised 537 adults with early type 2 diabetes to retatrutide 4, 9 or 12 mg or placebo for 40 weeks: HbA1c fell by 1.69, 1.86 and 1.94 percentage points versus 0.81 with placebo, and body weight by 11.5%, 13.9% and 15.3% versus 2.6%. Discontinuation for adverse events was 2–5%. As of September 2026 retatrutide is not approved in any country. Lilly has said it intends to submit a US application in early 2027 (later than first planned, citing manufacturing data requirements) and in August 2026 opened a pre-approval expanded-access programme for a defined patient group.
Side effects reported in trials
The adverse-event profile so far looks like the incretin class, with two glucagon-related additions. Gastrointestinal events — nausea, diarrhoea, vomiting, constipation — were the most common, dose-related, mostly mild to moderate, and reduced by the lower 2 mg starting dose. Heart rate rose in a dose-dependent way, peaking around 24 weeks and declining afterward. Skin sensitivity (dysesthesia) was reported more often than with placebo at higher doses. Long-term safety, cardiovascular outcomes and effects in broader populations are what the phase 3 programme exists to establish. The side-effects guide linked below goes through the published data, the class warnings that apply to approved incretins, and what is still unknown.
Retatrutide vs tirzepatide vs semaglutide
No trial has compared retatrutide head-to-head with either approved drug, so cross-trial comparisons are indicative only: retatrutide's phase 2 reached −24.2% at 48 weeks while still declining; tirzepatide's SURMOUNT-1 reached −20.9% at 72 weeks; semaglutide's STEP 1 reached −14.9% at 68 weeks. Populations, durations and dose-escalation schedules differ. What can be said structurally is that retatrutide is tirzepatide's architecture plus glucagon receptor activity, and that it has the longest half-life of the three. What cannot yet be said is anything about long-term safety or outcomes — semaglutide has cardiovascular, kidney and heart-failure outcome trials; retatrutide's are in progress.
“Research-grade” retatrutide online: what the label cannot tell you
Because retatrutide is unapproved, no pharmaceutical version exists outside clinical trials and Lilly's expanded-access programme. Everything sold online under the name is an unlicensed product of unknown provenance. Independent testing of such vials has repeatedly found under- or over-dosing, missing acylation, wrong peptides, and endotoxin contamination; a certificate of analysis showing HPLC purity does not establish sterility, correct side-chain attachment, or that the vial matches the certificate. Marketing these products for human use is illegal in the US, Canada and the EU. This profile exists to explain the science; it is not guidance on obtaining or using any product.
Sequence
One-letter sequence commonly cited for Retatrutide (educational; isoforms and modifications may differ):
YXQGTFTSDYSIXLDKKAQXAFIEYLLEGGPSSGAPPPS
X = non-canonical residue: Aib (α-aminoisobutyric acid) at positions 2 and 20; α-methyl-L-leucine at position 13. X marks a non-canonical residue — see the structure block below. (Plotted as alanine on the wheel.)
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
The A/L versus X differences denote Aib at positions 2 and 20 and alpha-methyl-leucine at 13. The Lys17 lipid chain and C-terminal amide are part of the form; the letter-only backbone is not an unmodified peptide. The matching PubChem CID supports this parent-form mass.
- Molecular form
- Retatrutide, amidated lipidated 39-residue parent peptide
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Amide
Average reference mass · Molecular identity assessment: 2026-10-05
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-09-06
- PubChem molecular record · 2026-09-06
- NIH GSRS retatrutide parent record (UNII NOP2Y096GV) · 2026-10-05
Y-[Aib]-Q-G-T-F-T-S-D-Y-S-I-[αMeLeu]-L-D-K-K(C20 diacid-γGlu-OEG)-A-Q-[Aib]-A-F-I-E-Y-L-L-E-G-G-P-S-S-G-A-P-P-P-S-NH2
- Molecular formula
- C221H342N46O68
- Average reference mass
- ≈ 4,731
- Plasma half-life
- ≈ 6 days
- Receptors
- GIP receptor, GLP-1 receptor and glucagon receptor. In vitro the molecule is GIPR-favouring, with GLP-1R activity somewhat lower than native GLP-1 and glucagon receptor activity lower still — a balance chosen so glucagon's energy-expenditure effect is captured without driving glucose up
- Backbone
- GIP-derived 39-residue scaffold with the exendin-4 C-terminal tail (…G-G-P-S-S-G-A-P-P-P-S) — the same architecture as tirzepatide
- Lipidation
- Eicosanedioic acid (C20 fatty diacid) → γ-glutamate → one OEG unit → ε-amine of Lys17
- C-terminus
- Amide
- Status
- Investigational (phase 3). Not approved in any jurisdiction as of September 2026; Eli Lilly has said it plans to file with the FDA in early 2027 and opened a pre-approval expanded-access programme in August 2026
| Position | Native | Analog | Purpose |
|---|---|---|---|
| Position 2 | Ala (GIP) | Aib | DPP-4 resistance |
| Position 3 | Glu (GIP) | Gln | Tunes the balance between the three receptors |
| Position 13 | Ala (GIP) | α-methyl-L-leucine | Helix stabilisation; contributes to glucagon receptor activity |
| Lys17 | — | Lys(C20 diacid-γGlu-OEG) | Albumin binding → ≈ 6-day half-life (tirzepatide acylates Lys20 instead) |
| Position 20 | Gln (GIP) | Aib | Second helix-stabilising residue |
| Residues 30–39 | GIP C-terminus | Exendin-4 tail (GGPSSGAPPPS-NH2) | GLP-1 receptor engagement and stability |
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-09-06.
Clinical development snapshot
ClinicalTrials.gov lists 33 registered studies with “Retatrutide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06260722 | Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glyc | Phase 3 | active not recruiting | 2026-09-28 |
| NCT07035093 | A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight and Chronic Low Back Pain | Phase 3 | active not recruiting | 2026-09-25 |
| NCT06383390 | The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obe | Phase 3 | active not recruiting | 2026-09-24 |
| NCT07165028 | A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease ( | Phase 3 | recruiting | 2026-09-22 |
| NCT05929066 | A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight | Phase 3 | completed | 2026-08-21 |
| NCT07629401 | Pre-approval Expanded Access of Retatrutide (LY3437943) | — | available | 2026-08-06 |
The incretin & metabolic co-agonist class at a glance
| Peptide | Receptors | Length | Mass (Da) | Half-life | Status |
|---|---|---|---|---|---|
| GLP-1 | GLP-1R | 30 aa | ≈ 3,297.6 | ≈ 1–2 min (DPP-4 cleavage + renal clearance) | Endogenous hormone — not a product |
| Liraglutide | GLP-1R | 31 aa | ≈ 3,751.2 | ≈ 13 h (once-daily dosing) | Approved: Victoza (2010, T2D), Saxenda (2014, weight) |
| Semaglutide | GLP-1R | 31 aa | ≈ 4,113.6 | ≈ 7 days (≈ 145–165 h in clinical PK studies) | Approved: Ozempic (2017, T2D), Rybelsus (2019, oral T2D), Wegovy (2021, weight) |
| Tirzepatide | GIPR + GLP-1R | 39 aa | ≈ 4,813.5 | ≈ 5 days (≈ 117 h) | Approved: Mounjaro (2022, T2D), Zepbound (2023, weight; 2024, obstructive sleep apnoea) |
| Retatrutide (this page) | GIPR + GLP-1R + GCGR | 39 aa | ≈ 4,731 | ≈ 6 days | Investigational (phase 3) |
| Cagrilintide | Amylin / calcitonin | 37 aa | ≈ 4,409 | ≈ 7–8 days (159–195 h across doses in the phase 1b study) | Investigational (phase 3, as CagriSema with semaglutide) |
| Survodutide | GCGR + GLP-1R | 29 aa | ≈ 4,232 | Supports once-weekly dosing (published population estimates are on the order of several days) | Investigational (phase 3: SYNCHRONIZE obesity programme; MASH programme) |
| Mazdutide | GCGR + GLP-1R | 34 aa | ≈ 4,476 | Supports once-weekly dosing (published estimates are on the order of several days) | Approved in China (NMPA): chronic weight management (27 June 2025) and type 2 diabetes (2025) |
| Amycretin | GLP-1R + amylin | — | — | Supports once-weekly subcutaneous dosing | Investigational (phase 2 results published 2025; later-phase trials under way) |
Verified from PubChem, IUPHAR and the primary discovery papers cited on each profile. Half-lives are approximate population means from published pharmacokinetics.
Retatrutide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Retatrutide, amidated lipidated 39-residue parent peptideAverage reference mass: 4,731 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Retatrutide
What is Retatrutide?+
Retatrutide (LY3437943) is an investigational 39-amino-acid peptide (C221H342N46O68, ≈4,731 Da) that activates three receptors — GIP, GLP-1 and glucagon. It shares its GIP-based scaffold and exendin-4 tail with tirzepatide, adds α-methyl-leucine and a second Aib, and carries a C20 fatty diacid on Lys17 for a half-life of about 6 days. In phase 2 it produced a mean weight change of −24.2% at 48 weeks; phase 3 trials are ongoing and it is not yet approved.
What Canadian product status is recorded for Retatrutide?+
Canadian product status for Retatrutide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Retatrutide?+
Retatrutide is commonly described as approximately 39 amino acids (Incretin triple agonist).
What is retatrutide?+
An investigational 39-amino-acid peptide from Eli Lilly (LY3437943) that activates the GIP, GLP-1 and glucagon receptors — a triple agonist. In phase 2 it produced −24.2% body weight at 48 weeks at the 12 mg dose. It is in phase 3 trials and is not yet approved.
Is retatrutide a peptide?+
Yes. It is a synthetic peptide with formula C221H342N46O68 and an average mass of about 4,731 Da, closely related to tirzepatide. It carries a C20 fatty diacid on lysine 17 and three non-canonical residues (two Aib, one α-methyl-leucine).
Is retatrutide approved by the FDA?+
No. As of September 2026 it is not approved in any country. Lilly has said it plans to submit to the FDA in early 2027; a pre-approval expanded-access programme opened in August 2026 for a defined patient group.
What is retatrutide's half-life?+
About 6 days, based on phase 1 pharmacokinetics. That supports once-weekly injection, the schedule used in all trials, and means steady state is reached after roughly 4–5 weekly doses.
How does retatrutide work?+
It combines GLP-1 receptor effects (appetite, gastric emptying, insulin), GIP receptor effects (insulin, adipose signalling, less nausea) and glucagon receptor effects (energy expenditure, liver fat oxidation). The three activities are balanced so glucose falls despite the glucagon component.
What is the amino acid sequence of retatrutide?+
Y-Aib-Q-G-T-F-T-S-D-Y-S-I-αMeLeu-L-D-K-K(acyl)-A-Q-Aib-A-F-I-E-Y-L-L-E-G-G-P-S-S-G-A-P-P-P-S-NH2, 39 residues, with the C20 diacid-γGlu-OEG side chain on lysine 17.
Is retatrutide “GLP-3”?+
No. There is no hormone called GLP-3; the nickname just means “three receptors”. Retatrutide's sequence is GIP-based, and it activates the GIP, GLP-1 and glucagon receptors.
Retatrutide vs tirzepatide — which produced more weight loss?+
There is no head-to-head trial. In separate studies, retatrutide reached −24.2% at 48 weeks (phase 2, still declining) and tirzepatide reached −20.9% at 72 weeks (SURMOUNT-1). Different populations and durations make this indicative only.
Further reading
- PharmacologyHow Does Retatrutide Work? Mechanism of Action at Three ReceptorsRetatrutide is one peptide that activates three metabolic hormone receptors — GIP, GLP-1 and glucagon. This guide explains what each receptor does, why the three activities are deliberately unbalanced, how the design keeps glucose falling despite glucagon agonism, and how the trial results line up with the mechanism.
- Clinical evidenceRetatrutide Side Effects: What the Clinical Trials Actually ReportedA sourced summary of retatrutide's adverse-event data from the phase 2 obesity and diabetes trials and the first phase 3 report — gastrointestinal effects, heart rate, skin sensitivity, discontinuations — plus the class warnings that apply to every incretin and what remains unknown.
- Clinical evidenceRetatrutide Dosing: Every Schedule Used in the Published Trials (Not a Protocol)The dose arms, starting doses, escalation steps and durations used in retatrutide's phase 2 obesity trial, phase 2 diabetes trial and phase 3 TRANSCEND-T2D-1, with the results each arm produced — plus a concentration calculator for the arithmetic of reconstitution. Descriptive, not prescriptive.
- ToolsRetatrutide Dosage Calculator: Reconstitution and Concentration Math (mg, mL, Units)An educational calculator for the arithmetic behind lyophilised retatrutide: how vial mass and diluent volume set the concentration, and what volume any amount corresponds to on a U-100 syringe. It computes; it does not recommend. Trial doses and their results are on the dosing guide.
- ComparisonRetatrutide vs Semaglutide (Ozempic, Wegovy): Triple Agonist vs GLP-1 — Structure, Half-Life, Trial DataSemaglutide is the approved GLP-1 analogue in Ozempic and Wegovy; retatrutide is an investigational GIP/GLP-1/glucagon triple agonist. This guide compares their sequences, receptors, half-lives, weight-loss and outcomes evidence, side effects and approval status — with no head-to-head trial to lean on.
- ComparisonRetatrutide vs Tirzepatide: Triple vs Dual Agonist — Structure, Half-Life, Trial DataRetatrutide and tirzepatide are 39-residue siblings built on the same GIP scaffold. This guide compares their sequences, receptor profiles, half-lives, phase 2/3 weight-loss data and approval status — with the caveat that no head-to-head trial exists.
- FoundationsWhat Is “GLP-3”? There Is No Such Hormone — the Name Means Retatrutide“GLP-3” and “GLP-3 peptide” are internet nicknames for retatrutide, the investigational GIP/GLP-1/glucagon triple agonist. This guide explains where the name came from, why it is scientifically wrong, what the real proglucagon-derived peptides are, and how to search the literature without it.
- PharmacologyGLP-1 and Incretin Peptide Half-Lives Compared: From 2 Minutes to 8 DaysA sourced table of the plasma half-lives of native GLP-1, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, retatrutide, cagrilintide and the newer co-agonists — and the three engineering strategies (DPP-4 resistance, albumin binding, Fc fusion) that stretch minutes into a week.
Related peptides
References & further reading
- 1.Jastreboff et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med
- 2.Rosenstock et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet
- 3.Urva et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet
- 4.Sanyal et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med
- 5.Coskun et al. (2025). Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Lancet Diabetes Endocrinol
- 6.Kanu et al. (2025). Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study. Diabetes Obes Metab
- 7.Urva et al. (2023). The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes Obes Metab
- 8.Li et al. (2024). Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discov
- 9.Bajaj et al. (2026). Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet
- 10.Doggrell (2023). Retatrutide showing promise in obesity (and type 2 diabetes). Expert Opin Investig Drugs
- 11.Doggrell (2023). Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?. Expert Opin Investig Drugs
- 12.Jakubowska et al. (2024). The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update. Endocrinol Metab (Seoul)
- 13.Gutgesell et al. (2024). Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes. Diabetes Ther
- 14.Katsi et al. (2025). Retatrutide-A Game Changer in Obesity Pharmacotherapy. Biomolecules
- 15.PubChem — compound summary for Retatrutide (CID 171390338)
- 16.Wikipedia — Retatrutide