A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Strongest weight loss of all weight-loss shots

    Proven benefit

    Energy & metabolism · Patients: obesity without diabetes · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    TRIUMPH-1 (2339 participants, 80 weeks): −17.6 to −25.0% versus −3.9% [4]. A direct comparison with tirzepatide or semaglutide is lacking; whether the weight returns after discontinuation has not been published. Both studies funded by Eli Lilly according to the abstract [3][4].[3]

  • Reduces liver fat

    Only proven in patients

    Energy & metabolism · Patients: fatty liver (MASLD) and obesity · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    Phase 2a substudy with 98 participants: liver fat lowered by up to 82.4% after 24 weeks (placebo +0.3%), up to 86% within the normal range; liver inflammation and fibrosis not an endpoint [6]. Several authors are employed by the manufacturer Eli Lilly [6].

  • Burns fat and spares muscle

    No benefit

    Muscle & performance · Patients: type 2 diabetes · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    Fat mass fell markedly, but the share of fat-free mass in the weight loss was similar to that with other weight-loss therapies; no advantage in muscle preservation; only 103 complete DXA measurements [5]. Funded by Eli Lilly [5].

  • Relieves knee pain

    Only proven in patients

    Recovery & healing · Patients: knee osteoarthritis and obesity · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    In TRIUMPH-1, the WOMAC pain score fell by 1.4 to 1.8 points more than with placebo (574 participants with knee osteoarthritis) [4]. Funded by Eli Lilly [4].

  • Lowers blood glucose

    Only proven in patients

    Energy & metabolism · Patients: type 2 diabetes · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    TRANSCEND-T2D-1 (537 participants, 40 weeks): HbA1c lowered by 0.88 to 1.12 percentage points more than with placebo [7]. Funded by Eli Lilly [7].

small studies: Every study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

manufacturer-funded: According to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

Mechanism of action

Evidence map: Retatrutide

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Retatrutide is a single peptide with agonist activity at three receptors: the glucagon receptor, the GIP receptor and the GLP-1 receptor; in the laboratory, activity at the glucagon and GLP-1 receptors is balanced and higher at the GIP receptor [1]. In obese mice, an increase in energy expenditure mediated via the glucagon receptor added to the reduced food intake via the GIP and GLP-1 receptors [1]. The half-life in humans is about 6 days; in a 12-week phase 1b study with 72 people with type 2 diabetes, blood glucose and weight fell [2]. All of these studies come from employees of the manufacturer.

In the phase 2 study with 338 adults with obesity, participants lost 8.7 to 24.2% depending on dose level in 48 weeks, versus 2.1% with placebo; heart rate rose in a dose-dependent manner, most strongly after 24 weeks [3]. The first phase 3 study, TRIUMPH-1, with 2339 adults with obesity without diabetes confirmed this: −17.6 to −25.0% after 80 weeks versus −3.9% with placebo; in knee osteoarthritis, pain fell, and in sleep apnea, the number of breathing interruptions fell [4]. In a DXA substudy in type 2 diabetes, mainly fat mass fell; the share of fat-free mass in the weight loss was similar to that of other weight-loss therapies [5]. In fatty liver, liver fat fell by up to 82% after 24 weeks, closely coupled to weight loss [6]. In the phase 3 study TRANSCEND-T2D-1, retatrutide lowered HbA1c in type 2 diabetes by 0.9 to 1.1 percentage points more than placebo [7]. Eli Lilly funded all of the studies.

Outside of studies, retatrutide is traded without approval as a “research peptide”. An analysis of Reddit posts identified 13,589 people who reported using it themselves; increased appetite, fatigue, nausea, insomnia and palpitations were frequently mentioned [8]. As with other compounds with GLP-1 activity, thyroid C-cell proliferation via the GLP-1 receptor has been described in rodents, though for older GLP-1 agonists [9].

Targets

TargetTypeActionKey dataEvidence
Glucagon receptorReceptorAgonistActivity similar to that at the GLP-1 receptor (laboratory) Laboratory[1]
GIP receptorReceptorAgonisthighest activity of the three receptors (laboratory) Laboratory[1]
GLP-1 receptorReceptorAgonist Laboratory[1]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismmodulated · Energy expenditure ↑ via the glucagon receptor (mouse); marked weight loss in humans (RCT)[1][4]
  • Insulin · glucosemodulated · HbA1c lowered by 0.9–1.1 percentage points more than with placebo in type 2 diabetes (RCT)[2][7]
  • Inflammation · oxidativeno data
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Subcutaneous (under the skin) · Weekly injection (investigational drug in studies)

    Dose-proportional pharmacokinetics, half-life about 6 days [2]; weight effect measurable up to day 43 after a single dose [1]. No published bioavailability found.

    Human, randomised

  • Subcutaneous (under the skin) · “Research peptide” from the gray market (powder vials)

    Not approved, content and purity uncontrolled; the FDA warns against such products [8]. An Australian analysis of the composition of such products was found but not read.

    Human, non-randomised

Human studies

  • TRIUMPH-1: obesity, knee osteoarthritis, sleep apnea

    RCT, double-blind, placebo-controlled, phase 3 · Patients: obesity without diabetes · n = 2339 · 80 weeks

    Measured: Weight change, WOMAC pain, apnea-hypopnea index

    Result: −17.6 to −25.0% versus −3.9%; knee pain and breathing interruptions lowered more than with placebo.[4]

    Human, randomised

  • Phase 2: obesity

    RCT, double-blind, placebo-controlled · Patients: obesity or overweight with a comorbidity · n = 338 · 48 weeks

    Measured: Weight change

    Result: −8.7 to −24.2% versus −2.1%; dose-dependent rise in heart rate.[3]

    Human, randomised

  • TRANSCEND-T2D-1: type 2 diabetes

    RCT, double-blind, placebo-controlled, phase 3 · Patients: type 2 diabetes · n = 537 · 40 weeks

    Measured: HbA1c, body weight

    Result: HbA1c −0.88 to −1.12 percentage points versus placebo; weight −11.5 to −15.3% versus −2.6%.[7]

    Human, randomised

  • Liver fat in fatty liver

    RCT, double-blind, placebo-controlled (phase 2 substudy) · Patients: fatty liver (MASLD) and obesity · n = 98 · 48 weeks (endpoint after 24 weeks)

    Measured: Liver fat (MRI)

    Result: −42.9 to −82.4% versus +0.3%.[6]

    Human, randomised

  • Body composition in type 2 diabetes

    RCT, double-blind, substudy with placebo and dulaglutide · Patients: type 2 diabetes · n = 189 · 36 weeks

    Measured: Fat mass (DXA)

    Result: Fat mass up to −26.1%; share of fat-free mass in the weight loss as with other therapies.[5]

    Human, randomised

  • Self-reports on Reddit

    cross-sectional analysis of social media posts · healthy people and patients without medical supervision (self-administration) · n = 13589 · Posts 2023–2025

    Measured: self-reported complaints

    Result: Frequent: increased appetite (17.1%), fatigue (15.2%), nausea (11.6%), insomnia (6.1%).[8]

    Human, non-randomised

Risks and warnings

  • No approval, uncontrolled gray market products

    Sold directly to consumers as a “research peptide”; identity, purity and amount uncontrolled; the FDA warns [8].

    Human, non-randomised

  • Rise in heart rate

    Dose-dependent, strongest after 24 weeks, then declining [3]; palpitations are among the frequently self-reported complaints [8].

    Human, randomised

  • Gastrointestinal complaints

    Most common side effects in all studies, dose-dependent, less frequent with a lower starting dose level [3][4][7].

    Human, randomised

  • Unknown long-term safety

    Longest published treatment duration 80 weeks; no endpoint studies on heart and vessels [4].

    No data

  • Thyroid C cells (animal finding, class)

    Shown in mice for older GLP-1 agonists; not tested here for retatrutide [9].

    Animal study

Fact check: common claims

  • not supported

    “Retatrutide works more strongly than tirzepatide”

    TRIUMPH-1 shows a large effect versus placebo [4]; a direct comparison with tirzepatide is lacking, and comparisons between different studies are uncertain.

  • not supported

    “Retatrutide spares muscle better than other weight-loss shots”

    The share of fat-free mass in the weight loss was similar to that with other therapies [5].

  • not supported

    ““Research” retatrutide from the internet is the same as in the studies”

    Gray market products are not approved and uncontrolled; the FDA warns against them [8].

  • partly supported

    “Retatrutide increases energy expenditure”

    Shown in mice via the glucagon receptor [1]; no published endpoint in humans found.

Pharmacokinetics

Absorption
Subcutaneous [2].
Half-life
About 6 days (human) [2].
Metabolism
Not verified.
Entry into the brain
Not verified.

Legal status

Germany
Not approved; investigational drug in clinical development [7][8].
EU
Not approved; investigational drug [7][8].
USA
Not approved; according to a study in JAMA Network Open, the FDA warns against unapproved products containing retatrutide that are sold directly to consumers, also labeled “research use only” [8].

Related compounds

Tirzepatidesame classSemaglutidesame class

Open questions

  • How much weight returns after discontinuation?
  • Does retatrutide lower cardiovascular events, and what does the rise in heart rate mean?
  • Does the glucagon component increase energy expenditure in humans?
  • What do gray market products actually contain?

References

  1. Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234–47.e9. doi:10.1016/j.cmet.2022.07.013 · PubMed
  2. Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, et al. 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. 2022;400(10366):1869–81. doi:10.1016/S0140-6736(22)02033-5 · PubMed
  3. Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389(6):514–26. doi:10.1056/NEJMoa2301972 · PubMed
  4. Jastreboff AM, Kaplan LM, Davies MJ, Wilding JPH, Ahmad NN, Murray M, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity. N Engl J Med. 2026. Online vor Druck. doi:10.1056/NEJMoa2604169 · PubMed
  5. Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, et al. 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. 2025;13(8):674–84. doi:10.1016/S2213-8587(25)00092-0 · PubMed
  6. Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037–48. doi:10.1038/s41591-024-03018-2 · PubMed
  7. Bajaj HS, Welch M, Shah P, Luna E, Jaouimaa FZ, Liu B, et al. 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. 2026;407(10546):2402–13. doi:10.1016/S0140-6736(26)00967-0 · PubMed
  8. Sehgal NKR, Tronieri JS, Rader B, Ungar L, Guntuku SC. Self-reported adverse effects among social media users taking nonapproved retatrutide. JAMA Netw Open. 2026;9(10):e2638929. doi:10.1001/jamanetworkopen.2026.38929 · PubMed
  9. Madsen LW, Knauf JA, Gotfredsen C, Pilling A, Sjögren I, Andersen S, et al. GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology. 2012;153(3):1538–47. doi:10.1210/en.2011-1864 · PubMed
How this profile was checked

Last reviewed: 2026-10-23. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-23); translation checked on 2026-10-26.

Checked

  • All abstracts read via PubMed (XML), DOIs and PMIDs reconciled with tools/pruefe_profile.py.
  • Key figures checked against abstracts: receptor profile, energy expenditure via GCGR (mouse), effect up to day 43 [1]; n = 72, t½ ≈ 6 days [2]; n = 338, −8.7 to −24.2 vs. −2.1%, heart rate [3]; n = 2339, −17.6 to −25.0 vs. −3.9%, WOMAC −1.4 to −1.8, AHI [4]; n = 189/103 DXA, fat mass up to −26.1% [5]; n = 98, liver fat up to −82.4%, up to 86% normal [6]; n = 537, HbA1c −0.88 to −1.12 [7].
  • In the full text (PMC13670051): 13,589 people with self-administration, frequencies of complaints, reference to the FDA warning about direct sales to consumers [8].
  • Funding: Eli Lilly for [2][3][4][5][6][7]; all authors of [1] employed by the manufacturer; [8] university-funded.
  • ClinicalTrials.gov: 34 entries for “retatrutide” (October 23, 2026), 32 of them from Eli Lilly.
  • October 26, 2026, precision flags (m004; rules in the guideline under “Number rule and precision flags”, implementation by Claude pending confirmation by Tilman): “Strongest weight loss of all weight-loss shots”: manufacturer-funded – [3] and [4] “Funded by Eli Lilly” according to the abstract. “Reduces liver fat”: “kleine_studien”, manufacturer-funded – [6] 98 randomized (abstract: “participants (n = 98) were randomly assigned”); several authors with an Eli Lilly affiliation (PubMed). “kleine_studien” added after the cross-check of October 26, 2026. “Burns fat and spares muscle”: manufacturer-funded – [5] several authors employed by Eli Lilly according to the conflict-of-interest statement. “Relieves knee pain”: manufacturer-funded – [4] “Funded by Eli Lilly” according to the abstract. “Lowers blood glucose”: manufacturer-funded – [7] several authors employed by Eli Lilly according to the conflict-of-interest statement. Cross-check October 26, 2026: evidence for the flags (participant numbers, direction, funding) incorporated into the begruendung and rechecked against abstracts or full texts.

Not verified

  • ClinicalTrials.gov contains an entry from the sponsor “Hudson Biotech” (NCT07467447, “Effect of LY3437943 Versus Placebo …”); not used as evidence, per instruction.
  • Composition of gray market products: Piatkowski et al. 2026 (Drug Alcohol Rev, “Composition and Labelling Accuracy of Products Sold as Retatrutide in Australia”) found, but neither abstract nor full text readable.
  • Wording of the FDA warning documented only via [8], not read directly.
  • Chemistry (molecular formula, SMILES): not found in PubChem.
  • Dysesthesia signal (abnormal skin sensations) from press releases on TRIUMPH-4 not found in a peer-reviewed source, therefore not included.

No dosages, no sources of supply. This information does not replace medical advice.

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