# Retatrutide: full monograph (Retatrutide Bio)
> Source page: https://retatrutidebio.com/monograph

Status: undefined
Disclosure: Retatrutide is an investigational drug still in clinical trials. It is not FDA approved for any use; vials sold online are unapproved research chemicals.

## Key facts
- Status: undefined
- Route: Subcutaneous injection, once weekly (trial protocols)
- Single dose note: A body-weight reduction persisted up to day 43 after a single dose in the first-in-human study.
- Unpublished: No steady-state timing, absolute bioavailability, or special-population exposure data have been published; there is no label to supply them.
- Drug class: GIP + GLP-1 + glucagon triple receptor agonist (source: https://europepmc.org/article/MED/37366315)
- Development stage: Phase 3 (TRIUMPH and TRANSCEND programs) (source: https://clinicaltrials.gov/api/v2/studies/NCT05929066)
- Best phase 2 obesity result: -24.2% mean weight at 48 weeks (12 mg) (source: https://europepmc.org/article/MED/37366315)
- Only published phase 3 result: T2D: HbA1c -1.94 points, weight -15.3% at 40 weeks (12 mg) (source: https://europepmc.org/article/MED/42250575)
- Half-life: About 6 days (source: https://europepmc.org/article/MED/36354040)
- Dosing in trials: Once weekly, subcutaneous (source: https://europepmc.org/article/MED/37366315)
- Phase 3 results posted: 0 of 14 registry records (source: https://clinicaltrials.gov/api/v2/studies?query.intr=retatrutide)
- Compounding: Prohibited under federal law (FDA) (source: https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)

## Overview
Retatrutide is a once-weekly injectable peptide that activates three metabolic hormone receptors at once: GIP, GLP-1, and glucagon 1 6 . In its 48-week phase 2 obesity trial, the 12 mg dose produced a 24.2% mean body-weight reduction 1 , a larger mean result than any published phase 3 figure for the approved incretin drugs 1 23 22 . That single sentence is why a gray market pre-sells this molecule, and it is exactly half the story. The other half: retatrutide is an unfinished experiment. It has zero Drugs@FDA records 26 , its 14 phase 3 registry records have zero posted results 30 39 , and FDA states it cannot be used in compounding under federal law and is not a component of any FDA-approved drug 25 . This page reports the spectacular numbers and their trial stage together, because the stage is part of the number.

## About retatrutide
Retatrutide began as Eli Lilly compound LY3437943, a single engineered peptide with agonist activity at the glucagon, GIP, and GLP-1 receptors 6 5 . PubChem records deposited under the name map to compound CID 171390338, molecular formula C221H342N46O68, molecular weight about 4731; the synonym list includes the street nickname Triple G 27 . The discovery paper published the full arc in 2022: balanced glucagon-receptor and GLP-1-receptor potency with greater GIP-receptor activity in vitro, weight reduction in obese mice, and a first-in-human single-dose study 6 . From there the program moved fast: a phase 1b trial in type 2 diabetes published in 2022 5 , twin phase 2 trials in obesity and diabetes published in 2023 1 2 , a liver-disease substudy in 2024 4 , and a phase 3 program (TRIUMPH for obesity, TRANSCEND for diabetes and kidney disease) whose first publication appeared in June 2026 10 3 .

## Regulatory status: not a drug you can be prescribed
No. A Drugs@FDA search for retatrutide returns zero records: no product, no label, no approved use 26 . FDA's position goes further than not-yet-approved. Its unapproved-GLP-1 page states that retatrutide cannot be used in compounding under federal law, is not a component of any FDA-approved drug, and has not been found safe and effective for any condition 25 . Unlike semaglutide or tirzepatide, there is no lawful compounded version of retatrutide at any pharmacy, anywhere in the US 25 . FDA has backed the statement with enforcement: warning letters to telehealth companies marketing retatrutide directly to consumers, to active-ingredient distributors selling it to compounders, and to outsourcing facilities repackaging it 25 . It has also warned companies selling retatrutide labeled 'for research purposes' or 'not for human consumption' while shipping it to consumers with dosing instructions 25 .

## Mechanism of action: what the third receptor adds
Semaglutide activates one receptor (GLP-1). Tirzepatide activates two (GIP and GLP-1). Retatrutide activates those two plus the glucagon receptor 1 6 . In vitro it shows balanced glucagon- and GLP-1-receptor activity with greater GIP-receptor activity 6 , and cryo-EM structures of the peptide engaging all three receptors were published in 2024 16 . The glucagon component is the interesting and the double-edged part. In obese mice, weight loss was augmented by glucagon-receptor-mediated increases in energy expenditure stacked on top of the calorie-intake reduction driven by the GIP and GLP-1 receptors 6 . A 2026 IUPHAR review is blunt about the evidence level: the energy-expenditure mechanism rests largely on preclinical rodent data, and clinical data for glucagon-receptor agonism are extremely limited 21 . A dedicated human calorie-intake and energy-expenditure trial (85 participants) completed in August 2025; no results are posted yet 46 . What is measured in humans: participants on 4 mg or more reported less hunger and less disinhibited eating than placebo, and those changes correlated with weight reduction 20 . A 2023 Lilly report also documents delayed gastric emptying, per its title 7 . The glucagon receptor is also expressed in liver, which is one hypothesis behind the unusually large liver-fat reductions in the MASLD substudy, and it is a candidate explanation for the heart-rate increases covered below 4 1 .

## Clinical evidence
Every published human trial, the key substudies and analyses, and the flagship phase 3 registry rows are in the table below, each row species-labeled and linked to its source. Three results define the published record. Obesity, phase 2: 24.2% mean weight reduction at 48 weeks on 12 mg, with every 12 mg participant losing at least 5% and 83% losing at least 15% 1 . Type 2 diabetes, phase 3 (the only phase 3 published so far): HbA1c down 1.94 points and weight down 15.3% at 40 weeks on 12 mg 3 . Liver disease, phase 2a: liver fat down 82.4% at 24 weeks on 12 mg, with 86% of participants reaching normal liver fat 4 . Independent syntheses agree on direction and on rank: a meta-analysis of four RCTs found dose-dependent effects maximal at 12 mg 17 , and a Bayesian network meta-analysis of 19 trials found retatrutide had the highest odds of 15%-or-greater weight loss among the compared drug classes, alongside the highest adverse-event risk 19 . Blood pressure and lipids improved across trials in a 2026 meta-analysis (systolic pressure down 6.79 mmHg; triglycerides down 40.90 mg/dL) 18 . Kidney measures moved favorably in post hoc analyses (albuminuria down about a third at 12 mg) 9 , and a fat-versus-lean substudy found the proportion of lean-mass loss similar to other obesity treatments 8 .

## Doses studied in trials (not dosing guidance)
There is no retatrutide dose a person can be prescribed, because there is no approved product and no prescribing label 26 25 . What exists are protocol doses given to monitored trial participants. The phase 2 obesity trial randomized participants to 1, 4, 8, or 12 mg once weekly for 48 weeks, with starting doses of 2 or 4 mg and stepwise escalation; the lower 2 mg start partially mitigated gastrointestinal side effects 1 . The phase 2 diabetes trial used 0.5 to 12 mg maintenance doses 2 , and the phase 3 TRANSCEND-T2D-1 trial used 4, 9, and 12 mg 3 . A dedicated phase 3b trial comparing escalation schemes (TRIUMPH-9) is running through 2028, which means the sponsor itself is still working out optimal titration 38 . This site publishes no dose calculator and no titration planner for retatrutide, and explains why on the tools page: with no approved dose, no label, and a federal compounding prohibition, a dosing tool would be an instruction manual for an unlawful product 25 .

## What side effects were reported in trials?
The consistent finding across every trial is gastrointestinal: nausea, diarrhoea, vomiting, and constipation, dose-related, mostly mild to moderate, and partially mitigated by a lower starting dose 1 2 . In the phase 2 diabetes trial, GI events affected 35% of retatrutide participants overall (13% to 50% by dose group) versus 13% on placebo, with no severe hypoglycaemia and no deaths 2 . In phase 3 TRANSCEND-T2D-1, GI events again led, subsided over time, and drove discontinuation in 2 to 5% of retatrutide participants versus 0% on placebo; two deaths occurred, both in the 4 mg group and judged unrelated to study drug 3 . Two signals deserve their own lines. First, heart rate: dose-dependent increases peaked at 24 weeks and declined thereafter in the phase 2 obesity trial 1 ; the cardiovascular section below covers what is and is not known. Second, skin sensations: a 2026 pharmacovigilance analysis of the WHO global database concluded its data strengthen evidence for dysesthesias (abnormal skin sensations, including burning) with GLP-1-receptor-agonist therapies, describes them as dose-dependent, and states such events were already observed in clinical trials of semaglutide, tirzepatide, and retatrutide; discontinuation was usually followed by resolution 12 . The honest safety headline is not any single event. It is the denominator: the entire published human safety record covers roughly 1,200 trial participants followed for 12 to 48 weeks under medical monitoring 1 2 3 5 . There is no label, no long-term file, and no pharmacovigilance system for the gray-market vials people actually inject 26 25 .

## Heart rate up, blood pressure down: the cardiovascular ledger
Both directions are real and both are cited. Down: a 2026 meta-analysis of the randomized trials found systolic blood pressure fell 6.79 mmHg, diastolic 2.46 mmHg, total cholesterol 21.88 mg/dL, LDL cholesterol 13.10 mg/dL, and triglycerides 40.90 mg/dL versus control 18 . Up: dose-dependent heart-rate increases that peaked at 24 weeks and declined thereafter in the 48-week obesity trial 1 . Glucagon-receptor agonism is a mechanistic candidate for that increase, but the mechanism literature is largely preclinical 21 . Whether the net effect helps or harms cardiovascular outcomes is exactly what no one knows yet. Semaglutide has answered this question for itself: a 20% relative reduction in major adverse cardiovascular events in the 17,604-patient SELECT trial 24 . Retatrutide's answer is scheduled, not known: TRIUMPH-Outcomes (NCT06383390), an event-driven trial in about 10,000 adults with atherosclerotic cardiovascular disease and/or chronic kidney disease, has an estimated primary completion of February 2029 39 .

## Who was studied, and who was not
The standard answer for an approved drug comes from its label's contraindications. Retatrutide has no label, so that answer does not exist for anyone 26 . What can be said honestly: the published trials enrolled adults only, under protocol entry criteria: BMI 30 or higher (or 27 to under 30 with a weight-related condition) in the obesity trial 1 ; HbA1c 7.0 to 10.5% and BMI 25 to 50 in the phase 2 diabetes trial 2 ; HbA1c 7.0 to 9.5% and BMI 23 or higher in the phase 3 diabetes trial 3 . Everyone outside those windows, including anyone pregnant, under 18, or with significant comorbidities excluded by protocol, has essentially no published exposure data. Because there is no approved product, there is also no validated guidance for drug interactions, kidney or liver dose adjustment, or use in any special population. Those chapters get written during and after regulatory review, which has not happened 26 25 .

## The TRIUMPH and TRANSCEND timeline, from the registry
No one outside Lilly and FDA can date an approval, and this site will not guess. What the public record shows, with registry dates: the TRIUMPH registrational program's four core trials (over 5,800 participants, basket design spanning obesity, obstructive sleep apnea, and knee osteoarthritis) are described in a 2026 design paper 10 . TRIUMPH-4 reached primary completion in November 2025 33 ; TRIUMPH-1 in April 2026 30 ; TRIUMPH-3 in April 2026 32 ; TRIUMPH-2 in June 2026 31 . All four are marked completed, and none has posted results to the registry as of August 14, 2026 30 31 32 33 . The first phase 3 publication anywhere in the program is TRANSCEND-T2D-1, in type 2 diabetes, in The Lancet in June 2026 3 . Two more signals worth knowing: ClinicalTrials.gov lists a pre-approval expanded access record for retatrutide in obesity and obesity-related complications, status Available 44 , a step The BMJ covered in August 2026 15 ; and later-readout trials run to 2027 through 2030 (head-to-head versus tirzepatide, November 2026 34 ; maintenance of weight reduction, 2028 35 ; cardiovascular outcomes, 2029 39 ; liver-disease master protocol, 2030 47 ). The full registry table with every date is below and on the tools page.

## The vials sold online
Unknown, and that is the point. FDA warns that illegally marketed GLP-1-class drugs may be counterfeit and could contain the wrong ingredients, harmful ingredients, or too little, too much, or no active ingredient at all 25 . Sellers label vials 'for research purposes' or 'not for human consumption' while shipping them to consumers with dosing instructions, a practice FDA has issued warning letters over 25 . The composition question has reached the scientific literature: a 2026 peer-reviewed letter reports formal testing of the composition and labelling accuracy of products sold as retatrutide in Australia 13 , and The BMJ ran a fact check on a reported death after use of the unapproved injection 14 . Two structural facts separate retatrutide's gray market from semaglutide's or tirzepatide's. First, there is no lawful compounded version at all: FDA states retatrutide cannot be used in compounding under federal law 25 . Second, there is no reference product to compare a vial against: no approved manufacturing standard, no label, no lot-release oversight 26 . Every real trial result on this page came from pharmaceutical-grade material given under medical monitoring inside a protocol; none of it validates anything sold from a website 1 .

## Pharmacokinetics
The published human pharmacokinetics come from the phase 1b multiple-ascending-dose trial: exposure was dose proportional, and the half-life was approximately 6 days, which is the basis for once-weekly subcutaneous dosing across the entire program 5 . After a single dose in the first-in-human study, a body-weight reduction persisted up to day 43 6 . No steady-state timing, absolute bioavailability, or exposure-by-population figures have been published in the abstracts of record; those chapters normally arrive with a regulatory label, which does not exist 26 .

## What we don't know yet
The list is long because the program is unfinished. No phase 3 obesity efficacy or safety results have been published or posted; the only phase 3 publication is 40-week diabetes monotherapy data 3 , and all 14 phase 3 registry records show hasResults false 30 39 . The longest published randomized exposure is 48 weeks 1 , so durability, plateau behavior, and year-two effects are unmeasured. What happens on stopping is unstudied for retatrutide; the maintenance-of-weight-reduction trial reads out around 2028 35 . Whether the heart-rate increase 1 matters for events, and whether the blood-pressure and lipid improvements 18 translate into fewer heart attacks and strokes, waits on TRIUMPH-Outcomes around February 2029 39 . The energy-expenditure mechanism attributed to the glucagon receptor is demonstrated in rodents, not yet in published human data 6 21 ; the human study is completed but unposted 46 . There is no approval anywhere in the US record, no prescribing label, no validated dose, and no lawful compounding pathway 26 25 . And nothing on this page describes the vials sold online, whose contents are unverified by any regulator 25 .

## References
Rendered from the machine-readable citation manifest; every numbered reference resolves to a peer-reviewed journal record (PMC or Europe PMC primary), an FDA page or openFDA API record, ClinicalTrials.gov, or PubChem.

## Frequently asked questions
Citations and FAQ render from the numbered manifests on this page.

## Related
Citations and FAQ render from the numbered manifests on this page.

## Study results
| Study | Species/model | n | Duration | Outcome | Effect size |
| --- | --- | --- | --- | --- | --- |
| Phase 2 obesity trial (https://europepmc.org/article/MED/37366315) | human (Randomized, double-blind, placebo-controlled, 7-arm dose-ranging) | 338 | 48 weeks | Percent change in body weight (primary at 24 weeks) | -24.2% (12 mg), -22.8% (8 mg), -17.1% (4 mg), -8.7% (1 mg) vs -2.1% placebo at 48 weeks; 100%/93%/83% of 12 mg reached >=5/>=10/>=15% loss |
| Phase 2 type 2 diabetes trial (https://europepmc.org/article/MED/37385280) | human (Randomized, double-blind, double-dummy, placebo- and dulaglutide-controlled) | 281 | 36 weeks (primary at 24) | HbA1c change (primary); body weight (secondary) | HbA1c -2.02 points (12 mg) vs -0.01 placebo and -1.41 dulaglutide at 24 weeks; weight -16.94% (12 mg) vs -3.00% placebo at 36 weeks |
| TRANSCEND-T2D-1 (first published phase 3) (https://europepmc.org/article/MED/42250575) | human (Randomized, double-blind, placebo-controlled monotherapy trial) | 537 | 40 weeks | HbA1c change (primary); percent weight change (key secondary) | HbA1c -1.94 (12 mg), -1.86 (9 mg), -1.69 (4 mg) vs -0.81 placebo; weight -15.3%/-13.9%/-11.5% vs -2.6%; all p<0.0001 |
| MASLD liver-fat substudy of the obesity trial (https://pmc.ncbi.nlm.nih.gov/articles/PMC11271400/) | human (Randomized, double-blind, placebo-controlled substudy; MRI-measured liver fat) | 98 | 48 weeks (primary at 24) | Relative change in liver fat at 24 weeks | -82.4% (12 mg), -81.4% (8 mg) vs +0.3% placebo; normal liver fat (<5%) in 86% (12 mg) vs 0% placebo |
| Body-composition (DXA) substudy of the diabetes trial (https://europepmc.org/article/MED/40609566) | human (Prespecified DXA substudy of the randomized diabetes trial) | 189 | 36 weeks | Percent change in total body fat mass | Fat mass -26.1% (pooled 8 mg), -23.2% (12 mg) vs -4.5% placebo, -2.6% dulaglutide; lean-loss proportion similar to other obesity treatments |
| Kidney-parameters post hoc analysis of both phase 2 trials (https://pmc.ncbi.nlm.nih.gov/articles/PMC12231004/) | human (Post hoc analysis of two randomized placebo-controlled trials) | 619 (281 T2D + 338 obesity) | 36-48 weeks | Urine albumin-to-creatinine ratio; eGFR | UACR -37.0% (12 mg, T2D) and -31.5% (12 mg, obesity) vs placebo; eGFR +8.5 ml/min per 1.73 m2 (12 mg) in obesity, unchanged in T2D |
| Phase 1b multiple-ascending-dose trial (T2D) (https://europepmc.org/article/MED/36354040) | human (Randomized, double-blind, placebo-controlled MAD; dulaglutide reference arm) | 72 | 12 weeks | Safety/tolerability (primary); PK, glucose, weight | Half-life approximately 6 days, dose-proportional PK; weight up to -8.96 kg placebo-adjusted; TEAEs 63% vs 54% placebo, GI most frequent |
| Discovery pharmacology (receptor profile; obese-mouse efficacy) (https://europepmc.org/article/MED/35985340) | mouse and in vitro (In vitro receptor pharmacology; diet-induced obese mice) | n/a (preclinical) | n/a | Receptor activity balance; body weight; energy expenditure | Balanced GCGR/GLP-1R with greater GIPR activity in vitro; in obese mice, weight loss augmented by GCGR-mediated energy expenditure on top of intake reduction |
| Phase 1 single-ascending-dose study (healthy adults) (https://europepmc.org/article/MED/35985340) | human (Single-ascending-dose first-in-human study) | 45 | Single dose, followed to day 43+ | Safety, tolerability, PK | Safety profile similar to other incretins; weight reduction persisted to day 43 after a single dose |
| Cryo-EM structures at GLP-1R, GIPR, and GCGR (https://pmc.ncbi.nlm.nih.gov/articles/PMC11255275/) | in vitro (Cryo-EM structural pharmacology) | n/a (structures) | n/a | Structural basis of triple agonism | Structures of retatrutide engaging each of its three receptors (title-anchored; abstract not openly indexed) |
| Appetite and eating-behavior analyses (diabetes trial) (https://pmc.ncbi.nlm.nih.gov/articles/PMC12587234/) | human (Appetite VAS and Eating Inventory during the randomized diabetes trial) | 275 | 36 weeks | Appetite, hunger, disinhibition scores | Greater reductions in appetite, hunger, prospective food consumption at >=4 mg vs placebo; hunger and disinhibition reductions correlated with weight change (r = 0.28-0.36) |
| Systematic review and meta-analysis of retatrutide RCTs (https://europepmc.org/article/MED/39817343) | n/a (meta-analysis of human RCTs) (SR/MA pooling 4 randomized controlled trials) | 4 RCTs | n/a | Efficacy and safety across outcomes | Dose-dependent effects, maximal at 12 mg; safety comparable to control in pooled analysis |
| Blood pressure and lipids meta-analysis (https://europepmc.org/article/MED/42371360) | n/a (meta-analysis of human RCTs) (SR/MA of randomized controlled trials) | RCT pool (random-effects) | n/a | Blood pressure; lipid panel | SBP -6.79 mmHg; DBP -2.46; total cholesterol -21.88 mg/dL; LDL-C -13.10; triglycerides -40.90; HDL-C unchanged |
| Bayesian network meta-analysis of incretin drugs (https://europepmc.org/article/MED/40685589) | n/a (meta-analysis of human RCTs) (NMA of 19 RCTs, 29,506 adults) | 29,506 (19 RCTs) | >=36 weeks | Weight-loss thresholds; adverse events | Retatrutide: highest odds of >=15% weight loss (OR 54.6) and highest adverse-event risk among compared classes |
| Dysesthesia pharmacovigilance analysis (VigiBase) (https://pmc.ncbi.nlm.nih.gov/articles/PMC13194321/) | human (pharmacovigilance reports) (Disproportionality analysis of the WHO VigiBase database plus case-narrative review) | Global report database | n/a | Dysesthesia, hyperaesthesia, burning skin sensations | Dose-dependent dysesthesia with GLP-1-receptor-agonist therapies; events already observed in clinical trials of semaglutide, tirzepatide, and retatrutide; discontinuation usually followed by resolution |
| TRIUMPH-1 (registrational obesity trial) (https://clinicaltrials.gov/api/v2/studies/NCT05929066) | human (Randomized, double-blind, placebo-controlled master protocol (OSA and knee-OA baskets nested)) | 2335 | Primary completion 2026-04-06 (actual) | Percent change in body weight (per design paper) | No results posted to the registry and none published; hasResults = false as of 2026-08-14 |
| TRIUMPH-5 (head-to-head vs tirzepatide) (https://clinicaltrials.gov/api/v2/studies/NCT06662383) | human (Randomized, double-blind, active-comparator trial) | 800 (estimated) | Estimated primary completion 2026-11 | Efficacy and safety vs tirzepatide (per registry title) | First direct retatrutide-vs-tirzepatide comparison; no results; hasResults = false as of 2026-08-14 |
| TRIUMPH-Outcomes (cardiovascular and kidney outcomes) (https://clinicaltrials.gov/api/v2/studies/NCT06383390) | human (Randomized, double-blind, placebo-controlled, event-driven outcomes trial in ASCVD and/or CKD) | 10,000 (estimated) | Estimated primary completion 2029-02 | Major adverse cardiovascular events; kidney outcomes | The trial that will answer the outcomes question; no results; hasResults = false as of 2026-08-14 |

## What we do not know yet
What we don't know yet: no phase 3 obesity efficacy or safety results have been published or posted to the registry; the only published phase 3 data are 40-week type 2 diabetes monotherapy results (June 2026). The longest published randomized exposure is 48 weeks, so durability and year-two effects are unmeasured, and what happens on stopping is unstudied for retatrutide (the maintenance trial reads out around 2028). Whether the dose-dependent heart-rate increase matters for events, and whether the blood-pressure and lipid improvements translate into fewer heart attacks and strokes, waits on TRIUMPH-Outcomes around February 2029. The glucagon-receptor energy-expenditure mechanism is demonstrated in rodents, not in published human data. There is no FDA approval, no prescribing label, no validated dose, and no lawful compounding pathway; the contents of vials sold online are unverified by any regulator.

## Questions and answers
### How much weight did people lose on retatrutide in trials?
In the 48-week phase 2 obesity trial, mean weight change was -24.2% on 12 mg (n=338) vs -2.1% placebo. That is a phase 2 number: the completed phase 3 obesity trials have posted no results yet. The published phase 3 (diabetes) showed -15.3% at 40 weeks.

In the 48-week phase 2 obesity trial (338 adults), least-squares mean weight change was -24.2% on 12 mg, -22.8% on 8 mg, -17.1% on 4 mg, and -8.7% on 1 mg, versus -2.1% with placebo. Every participant on 8 or 12 mg lost at least 5%; 93% of the 12 mg group lost at least 10% and 83% lost at least 15%.The stage matters as much as the number: that is a phase 2 result in 338 people, not a phase 3 result in thousands. The phase 3 obesity trials (TRIUMPH-1 and -3, over 4,200 participants) are completed but have published nothing and posted no results as of August 14, 2026. In the published phase 3 diabetes trial, weight fell 15.3% at 40 weeks on 12 mg; people with type 2 diabetes consistently lose less in this drug class.

### Is retatrutide FDA approved?
No. Drugs@FDA holds zero retatrutide records, and FDA states retatrutide cannot be used in compounding under federal law and is not a component of any approved drug. It is an investigational molecule in phase 3 trials; vials sold online are unapproved research chemicals.

No. A Drugs@FDA search for retatrutide as an active ingredient returns zero records: no approved product exists for any use. FDA also states that retatrutide cannot be used in compounding under federal law, is not a component of any FDA-approved drug, and has not been found safe and effective for any condition.Retatrutide is an investigational drug still in clinical trials. It is not FDA approved for any use; vials sold online are unapproved research chemicals.

### When could retatrutide be approved?
Unknown; approval dates are not public records. The registry shows: all 4 core TRIUMPH phase 3 trials completed by June 2026, zero results posted; first phase 3 publication June 2026 (diabetes); a pre-approval expanded-access record now live. No sold vial is approved.

No public record answers that, and this site does not guess. What the registry shows: all four core TRIUMPH phase 3 trials are completed (primary completion dates November 2025 through June 2026) with no posted results; the first phase 3 publication (type 2 diabetes) appeared in June 2026; and a pre-approval expanded access record for obesity is live on ClinicalTrials.gov, a step The BMJ reported in August 2026. Later readouts run to 2029 (cardiovascular outcomes) and 2030 (liver disease).Until an approval actually happens, nothing sold anywhere is an approved retatrutide product.

### Is retatrutide stronger than tirzepatide?
No head-to-head data exist. Cross-trial: retatrutide -24.2% (phase 2, 48 wk, n=338) vs tirzepatide -20.9% (phase 3, 72 wk, n=2,539). The first direct trial, TRIUMPH-5, reads out around Nov 2026. And tirzepatide is approved; retatrutide is not.

No head-to-head results exist, so nobody knows yet. The cross-trial numbers, with their stages: retatrutide 12 mg produced -24.2% at 48 weeks in a phase 2 trial of 338 people; tirzepatide 15 mg produced -20.9% at 72 weeks in a phase 3 trial of 2,539 people. Different trials, durations, and populations; phase 2 effect sizes often shrink in phase 3. A network meta-analysis ranks retatrutide highest for 15%-or-greater loss, and also highest for adverse-event risk.The real answer is scheduled: TRIUMPH-5 (NCT06662383) is the first randomized retatrutide-versus-tirzepatide trial, with estimated primary completion in November 2026. The other difference is not close: tirzepatide is an FDA-approved medicine; retatrutide is not approved for anything.

### What does the glucagon receptor add?
Glucagon agonism adds energy expenditure to appetite suppression in mice, and may drive the outsized liver-fat reductions (-82.4% at 12 mg). In humans this mechanism is still unproven: the evidence is largely preclinical, and the human energy-expenditure trial has not posted results.

The third receptor is what separates retatrutide from tirzepatide (GIP + GLP-1) and semaglutide (GLP-1 only). In obese mice, glucagon-receptor activation added energy-expenditure-driven weight loss on top of the appetite reduction from the other two receptors. The glucagon receptor is also highly expressed in liver, and the liver-fat results in the MASLD substudy (down 82.4% at 12 mg) are among the program's most striking.The honest caveat comes from a 2026 IUPHAR review: the energy-expenditure mechanism rests largely on preclinical rodent data, and human clinical data for glucagon-receptor agonism are extremely limited. A human calorie-intake and energy-expenditure trial completed in August 2025 and has not posted results. Glucagon agonism is also a candidate mechanism for the dose-dependent heart-rate increase seen at 24 weeks.

### What is in the vials sold online as retatrutide?
Unknown. FDA warns such products may be counterfeit and may contain wrong or harmful ingredients, or too little, too much, or no active ingredient. Researchers have begun testing gray-market retatrutide vials. No approved reference product exists to compare against.

Nobody can tell you, and that is the problem. FDA warns that illegally marketed GLP-1-class drugs may be counterfeit and could contain the wrong ingredients, harmful ingredients, or too little, too much, or no active ingredient at all. 'Research use only' labels are a legal costume: FDA has warned companies selling retatrutide labeled that way while shipping it to consumers with dosing instructions.Independent scientists have begun testing what is actually sold: a 2026 peer-reviewed letter reports on the composition and labelling accuracy of products sold as retatrutide in Australia, and The BMJ ran a fact check on a reported death after use of the unapproved injection. Unlike semaglutide or tirzepatide, there is no approved reference product and no lawful compounded version to compare against: retatrutide cannot be used in compounding under federal law.

### What are retatrutide's side effects in trials?
Mostly dose-related GI events (nausea, vomiting, diarrhoea), mild to moderate in trials; discontinuation 2-5% vs 0% placebo in phase 3 diabetes. Also: heart-rate increases peaking at week 24 and a skin-sensation (dysesthesia) signal. No label, no long-term safety file.

Gastrointestinal events lead everywhere: dose-related nausea, diarrhoea, vomiting, and constipation, mostly mild to moderate, partially mitigated by a 2 mg starting dose. In the phase 2 diabetes trial they affected 35% of retatrutide participants versus 13% on placebo, with no severe hypoglycaemia and no deaths; in the phase 3 diabetes trial they subsided over time and drove discontinuation in 2 to 5% versus 0% on placebo.Beyond GI: dose-dependent heart-rate increases peaking at 24 weeks, and a pharmacovigilance signal for abnormal skin sensations (dysesthesia, including burning) reported with this drug class and described as already observed in trials of semaglutide, tirzepatide, and retatrutide. A network meta-analysis found retatrutide carried the highest adverse-event risk among compared incretin classes. The deeper caveat: the published safety record covers roughly 1,200 monitored trial participants for up to 48 weeks; there is no label and no long-term file.

### What did retatrutide do in type 2 diabetes trials?
Phase 2: HbA1c down up to 2.02 points, weight down up to 16.94%. Phase 3 (published June 2026, 537 adults): HbA1c -1.94, weight -15.3% at 40 weeks on 12 mg, no severe hypoglycaemia. This is the only retatrutide indication with published phase 3 data.

The phase 2 trial (281 adults, 36 weeks) cut HbA1c by up to 2.02 percentage points at 24 weeks versus 0.01 with placebo and 1.41 with dulaglutide 1.5 mg, with weight down up to 16.94% at 36 weeks. The phase 3 TRANSCEND-T2D-1 trial (537 adults, 40 weeks, monotherapy), published in The Lancet in June 2026, showed HbA1c down 1.69 to 1.94 points versus 0.81 with placebo and weight down 11.5 to 15.3% versus 2.6%, with no severe hypoglycaemia.This is the one indication where retatrutide already has published phase 3 evidence. Further phase 3 diabetes trials, including a head-to-head against semaglutide, have estimated primary completions in late 2026.

### What happened to liver fat in the trials?
In the randomized MASLD substudy (n=98), liver fat fell 81.4% (8 mg) and 82.4% (12 mg) vs +0.3% placebo at 24 weeks, and 86% of the 12 mg group reached normal liver fat. Phase 2a numbers; the phase 3 liver-disease trial runs to about 2030.

In the randomized MASLD substudy of the obesity trial (98 participants with at least 10% liver fat), mean relative liver-fat change at 24 weeks was -81.4% on 8 mg and -82.4% on 12 mg, versus +0.3% with placebo. Normal liver fat (below 5%) was reached by 79% of the 8 mg group and 86% of the 12 mg group, versus 0% on placebo.Those are phase 2a substudy numbers in a small group, not an approved liver indication. A phase 3 master-protocol trial in metabolic dysfunction-associated steatotic liver disease that includes retatrutide is recruiting, with estimated primary completion in 2030.

### Does retatrutide burn muscle along with fat?
In the DXA substudy, fat mass fell 26.1% (8 mg) vs 4.5% placebo at 36 weeks, and the proportion of lean-mass loss was similar to other obesity treatments. A phase 2 substudy finding in people with type 2 diabetes, not a general claim.

The DXA body-composition substudy of the diabetes trial measured exactly this. Total body fat mass fell 26.1% (pooled 8 mg) and 23.2% (12 mg) at 36 weeks, versus 4.5% with placebo and 2.6% with dulaglutide. The authors reported that the proportion of lean-mass loss to total weight loss was similar to other obesity treatments: in their words, reassurance that a greater share of lean mass is not lost despite the larger overall weight loss.Like everything else here, that is a phase 2 substudy finding, in people with type 2 diabetes, over 36 weeks.

### Is it legal to buy retatrutide online?
There is no lawful retail path in the US: retatrutide is unapproved and FDA states it cannot be used in compounding under federal law. Lawful access is inside the system: clinical trial enrollment, or the sponsor's expanded access program.

There is no lawful retail path to retatrutide in the US. It is not an approved drug, and FDA states it cannot be used in compounding under federal law, which closes the pathway that exists for some other unapproved substances. FDA has issued warning letters to telehealth companies marketing it, distributors selling the ingredient, and facilities repackaging it.The lawful ways to receive retatrutide are inside the system: enrollment in a clinical trial listed on ClinicalTrials.gov, or the sponsor's pre-approval expanded access program, whose registry record is live and whose eligibility is controlled by the sponsor and a treating physician.

### How many units of retatrutide should I take?
There is no valid answer: no approved product, no label, no established dose exists. Trial doses (1-12 mg weekly, monitored, pharmaceutical-grade) describe protocols, not website vials. That is why this site ships no retatrutide dose calculator.

This question has no answerable form: there is no approved retatrutide product, no prescribing label, and therefore no dose that exists outside a trial protocol. Trial doses (1 to 12 mg weekly, with 2 to 4 mg starting doses and stepwise escalation) were given to screened, monitored participants using pharmaceutical-grade material, none of which describes a vial from a website. Even the sponsor is still testing escalation schemes in a dedicated phase 3b trial running to 2028.That is why this site publishes no retatrutide dose calculator: with no approved dose and a federal compounding prohibition, a calculator would be an instruction manual for an unlawful and unverifiable product.

## References
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21. Elmendorf AJ, Yousefian M, Kim IM, et al. IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes. Pharmacol Res. 2026;223:108077. https://pmc.ncbi.nlm.nih.gov/articles/PMC12910462/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC12910462/)
22. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. https://europepmc.org/article/MED/33567185
23. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. https://europepmc.org/article/MED/35658024
24. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. https://europepmc.org/article/MED/37952131
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26. Drugs@FDA search: zero retatrutide records. The openFDA API query (products.active_ingredients.name:"retatrutide") returns NOT_FOUND by design; response archived in verification/openfda_drugsfda_reta.json, run 2026-08-14. https://www.accessdata.fda.gov/scripts/cder/daf/
27. PubChem compound record CID 171390338 (retatrutide substance depositions): molecular formula and weight via PUG REST, fetched 2026-08-14. https://pubchem.ncbi.nlm.nih.gov/compound/171390338
28. ClinicalTrials.gov NCT04881760: phase 2 trial of once-weekly LY3437943 (retatrutide) in obesity or overweight with weight-related comorbidities. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT04881760
29. ClinicalTrials.gov NCT04867785: phase 2 trial of LY3437943 (retatrutide) versus placebo and dulaglutide in type 2 diabetes. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT04867785
30. ClinicalTrials.gov NCT05929066: TRIUMPH-1, phase 3 master-protocol trial of retatrutide in obesity or overweight (with nested OSA and knee-OA baskets). Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT05929066
31. ClinicalTrials.gov NCT05929079: TRIUMPH-2, phase 3 trial of retatrutide in type 2 diabetes with obesity or overweight. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT05929079
32. ClinicalTrials.gov NCT05882045: TRIUMPH-3, phase 3 trial of retatrutide in severe obesity with cardiovascular disease. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT05882045
33. ClinicalTrials.gov NCT05931367: TRIUMPH-4, phase 3 trial of retatrutide in obesity or overweight with knee osteoarthritis. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT05931367
34. ClinicalTrials.gov NCT06662383: TRIUMPH-5, phase 3 head-to-head trial of retatrutide versus tirzepatide in obesity. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06662383
35. ClinicalTrials.gov NCT06859268: TRIUMPH-6, phase 3b trial of retatrutide in maintenance of weight reduction. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06859268
36. ClinicalTrials.gov NCT07035093: TRIUMPH-7, phase 3 trial of retatrutide in obesity or overweight with chronic low back pain. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT07035093
37. ClinicalTrials.gov NCT07232719: TRIUMPH-8, phase 3b trial of retatrutide in obesity or overweight. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT07232719
38. ClinicalTrials.gov NCT07357415: TRIUMPH-9, phase 3b trial of retatrutide dose-escalation schemes in obesity or overweight. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT07357415
39. ClinicalTrials.gov NCT06383390: TRIUMPH-Outcomes, phase 3 event-driven cardiovascular and kidney outcomes trial of retatrutide in ASCVD and/or CKD. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06383390
40. ClinicalTrials.gov NCT06354660: TRANSCEND-T2D-1, phase 3 trial of retatrutide versus placebo in type 2 diabetes (published in The Lancet, June 2026). Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06354660
41. ClinicalTrials.gov NCT06260722: phase 3 open-label trial of retatrutide versus semaglutide in type 2 diabetes. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06260722
42. ClinicalTrials.gov NCT06297603: phase 3 trial of retatrutide versus placebo in type 2 diabetes with moderate or severe chronic kidney disease. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06297603
43. ClinicalTrials.gov NCT05936151: TRANSCEND-CKD, phase 2b mechanistic trial of retatrutide on renal function in overweight or obesity with chronic kidney disease. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT05936151
44. ClinicalTrials.gov NCT07629401: pre-approval expanded access record for retatrutide (LY3437943), status Available. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT07629401
45. ClinicalTrials.gov NCT04143802: phase 1b multiple-ascending-dose trial of LY3437943 (retatrutide) in type 2 diabetes. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT04143802
46. ClinicalTrials.gov NCT06313528: phase 1 trial of retatrutide effect on calorie intake and energy expenditure in obesity. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT06313528
47. ClinicalTrials.gov NCT07165028: phase 3 master-protocol trial of multiple agents including retatrutide in metabolic dysfunction-associated steatotic liver disease. Record accessed Aug 2026. https://clinicaltrials.gov/api/v2/studies/NCT07165028
48. ClinicalTrials.gov API v2 snapshot for query.intr=retatrutide (archived 2026-08-13, re-verified 2026-08-14) https://clinicaltrials.gov/api/v2/studies?query.intr=retatrutide