Retatrutide

Dosing from the Literature

Published for fat loss: 4, 9 or 12 mg once a week for 80 weeks in Phase 3 (Jastreboff et al., 2026; Bellido et al., 2026), and 1 to 12 mg once a week for 48 weeks in Phase 2 (Jastreboff et al., 2023). Not published: the full results of TRIUMPH-3 and TRIUMPH-4; no dose is approved.

The doses below are the ones given in the Phase 2 trials (Jastreboff et al., 2023; Rosenstock et al., 2023) and in Lilly’s Phase 3 TRIUMPH and TRANSCEND-T2D trials (Jastreboff et al., 2026; Bellido et al., 2026; Bajaj et al., 2026). Retatrutide is not approved anywhere, so no labeled dose exists. This is research documentation, not medical advice.

What It Is

Retatrutide (LY3437943) is an investigational peptide from Eli Lilly that acts on three hormone receptors: those for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (Jastreboff et al., 2023). Online it is sometimes called “GLP-3”, but there is no human hormone by that name: the nickname stands for a drug that acts on three receptors (Coskun et al., 2022). It is not approved anywhere. Lilly is testing it in Phase 3 trials in obesity, type 2 diabetes, knee osteoarthritis pain, obstructive sleep apnea, chronic low back pain, heart and kidney outcomes, and fatty liver disease (Eli Lilly, September 29, 2026), and plans to submit it to the FDA in the first quarter of 2027 (Eli Lilly, July 23, 2026).

Its World Health Organization naming entry gives the structure: a chain of 39 amino acids that includes two units of 2-methylalanine (Aib) and one of 2-methyl-L-leucine, with a 20-carbon fatty diacid attached through a linker to lysine 17; the formula is C221H342N46O68 (WHO, 2022), a molecular weight of about 4,731 (KEGG DRUG, entry D12430). In people its half-life is about 6 days, which allows one injection a week under the skin (Urva et al., 2022; Sanyal et al., 2024).

What sets it apart from tirzepatide, which acts on the GIP and GLP-1 receptors (Zepbound label), is the glucagon receptor. Glucagon makes the liver release glucose into the blood; drug developers added glucagon-receptor action to raise energy expenditure, and a 2026 review says the glucose-lowering action of GLP-1 and GIP agonism can offset the rise in blood sugar (Elmendorf et al., 2026). The same review notes that glucagon-receptor agonists raise energy expenditure strongly in rodents, that the evidence in people is limited and comes from short infusion studies, and that whether weeks of glucagon-receptor action carry the same risks as short-term use remains to be seen (Elmendorf et al., 2026).

In the Phase 2 obesity trial, the 12 mg group lost 24.2% of body weight at 48 weeks, against 2.1% on placebo (Jastreboff et al., 2023); in the Phase 3 TRIUMPH-1, adults without diabetes on 12 mg lost 25.0% at 80 weeks, against 3.9% (Jastreboff et al., 2026). For scale, tirzepatide 15 mg gave 20.9% at 72 weeks in SURMOUNT-1, a trial of 2,539 adults with obesity or overweight and without diabetes (Jastreboff et al., 2022), and semaglutide 2.4 mg gave 14.9% at 68 weeks in STEP 1, a trial of 1,961 adults with obesity or overweight and without diabetes (Wilding et al., 2021); those are separate trials, of different lengths and with different participants, not head-to-head comparisons. The direct comparison with tirzepatide, TRIUMPH-5, is due to reach its primary completion in November 2026 (NCT06662383).

Mechanism of Action

Retatrutide is one peptide that acts on three receptors: GIP, GLP-1 and glucagon (Jastreboff et al., 2023). The points below are findings in cells, animals and the trials, each named.

• GLP-1R agonism (appetite) — In obese mice, the GLP-1 and GIP arms cut calorie intake (Coskun et al., 2022), and in people retatrutide delays gastric emptying (Urva et al., 2023). Semaglutide is a GLP-1 receptor agonist (Lincoff et al., 2023).
• GIPR agonism — In cell culture, retatrutide was 8.9 times as potent as natural GIP at the GIP receptor, and 0.3 and 0.4 times as potent as glucagon and GLP-1 at theirs (Sanyal et al., 2024). In obese mice, its GIP and GLP-1 arms together cut calorie intake (Coskun et al., 2022).
• GCGR agonism (energy expenditure, liver fat) — In obese mice, adding glucagon-receptor action raised energy expenditure and deepened weight loss (Coskun et al., 2022). In people with fatty liver, liver fat fell by up to 82.4% at 24 weeks, and the falls tracked weight loss and markers of better insulin sensitivity and lipid metabolism (Sanyal et al., 2024).
• Balanced potency profile — In the discovery paper, retatrutide acted more strongly at the GIP receptor than at the GLP-1 and glucagon receptors, which it activated about equally (Coskun et al., 2022). Despite the glucagon arm, HbA1c fell by up to 2.02% in 24 weeks in people with type 2 diabetes (Rosenstock et al., 2023).
• Gastric emptying delay — Retatrutide delays gastric emptying (Urva et al., 2023).
• Blood pressure and lipids — In TRIUMPH-4, retatrutide lowered non-HDL cholesterol, triglycerides and hsCRP, and systolic blood pressure by 14.0 mmHg on 12 mg (Eli Lilly, December 11, 2025).

What the Research Shows

The evidence runs from cell and mouse studies (Coskun et al., 2022) through Phase 1 and Phase 2 trials to five Phase 3 trials, three of them published (Jastreboff et al., 2026; Bellido et al., 2026; Bajaj et al., 2026). The points below summarize it by use; each trial is set out under Human Data.

• Discovery and preclinical (Coskun et al., 2022) — In cell assays, retatrutide acted about equally at the glucagon and GLP-1 receptors and more strongly at the GIP receptor. In obese mice it lowered body weight and improved blood sugar control, and its glucagon arm added a rise in energy expenditure to the cut in calorie intake from the GIP and GLP-1 arms (Coskun et al., 2022).
• Weight — In adults without diabetes, 24.2% lost at 48 weeks on 12 mg in Phase 2, against 2.1% on placebo (Jastreboff et al., 2023), and 25.0% at 80 weeks on 12 mg in the Phase 3 TRIUMPH-1, against 3.9% (Jastreboff et al., 2026). Lilly’s unpublished results: 22.6% at 80 weeks on 12 mg in adults with a BMI of 35 or more and established cardiovascular disease, with or without type 2 diabetes (TRIUMPH-3), and 28.7% at 68 weeks on 12 mg in adults with obesity or overweight and knee osteoarthritis, without diabetes (TRIUMPH-4), both by the efficacy estimand, which estimates the effect had everyone stayed on treatment (Eli Lilly, July 23, 2026; Eli Lilly, December 11, 2025).
• Type 2 diabetes — HbA1c fell by up to 2.02% at 24 weeks in Phase 2 (Rosenstock et al., 2023) and by 1.94% at 40 weeks on 12 mg in the Phase 3 TRANSCEND-T2D-1, against 0.81% on placebo (Bajaj et al., 2026). In adults with obesity and type 2 diabetes, weight fell 18.8% at 80 weeks on 12 mg, against 5.1% (Bellido et al., 2026).
• Knee osteoarthritis and sleep apnea — In TRIUMPH-1, WOMAC knee pain fell by 4.1 points on 12 mg, against 2.5 on placebo, in 574 adults with knee osteoarthritis, and apnea-hypopnea events fell by 32.1 an hour on 12 mg, against 9.6, in 243 with obstructive sleep apnea (intention-to-treat estimates; Jastreboff et al., 2026). TRIUMPH-2’s sleep apnea results have not yet been presented (Eli Lilly, September 29, 2026).
• Liver fat (Sanyal et al., 2024) — In 98 adults with fatty liver from the Phase 2 obesity trial, liver fat fell by 42.9% (1 mg) to 82.4% (12 mg) at 24 weeks, against a 0.3% rise on placebo, and was normal (under 5%) in 79% on 8 mg and 86% on 12 mg (Sanyal et al., 2024). A Phase 3 trial of liver outcomes in high-risk fatty liver disease is recruiting (NCT07165028).
• Body composition (Coskun et al., 2025) — In the Phase 2 type 2 diabetes trial, total fat mass fell by up to 26.1% at 36 weeks (8 mg), and the share of weight lost as lean mass was similar to other obesity treatments.
• Cardiovascular risk markers — In post hoc analyses of the two Phase 2 trials, relative to placebo, non-HDL cholesterol fell by up to 26.9%, apolipoprotein B by up to 24.2% and hsCRP by 54.8% in the obesity trial; hsCRP did not fall significantly in the diabetes trial (Ruotolo et al., 2026). Whether that means fewer heart attacks and strokes is what the cardiovascular and kidney outcomes trial will test (NCT06383390).
• Kidneys — TRANSCEND-CKD, a Phase 2b trial in 146 adults with overweight or obesity and chronic kidney disease, measured kidney filtration at 24 weeks (Heerspink et al., 2026); it was completed in October 2025, and no results are published (NCT05936151).
• Initial TRIUMPH program — Four Phase 3 registration trials: TRIUMPH-1 (obesity, with knee osteoarthritis and sleep apnea studied within it), TRIUMPH-2 (obesity with type 2 diabetes, with sleep apnea studied within it), TRIUMPH-3 (obesity with cardiovascular disease) and TRIUMPH-4 (obesity with knee osteoarthritis) (Giblin et al., 2026; Eli Lilly, September 29, 2026). Lilly has announced the main results of all four, apart from TRIUMPH-2’s sleep apnea trial (Eli Lilly, September 29, 2026); TRIUMPH-1 and TRIUMPH-2 are published (Jastreboff et al., 2026; Bellido et al., 2026). The registry gives the TRIUMPH name to later trials too, TRIUMPH-5 to TRIUMPH-9 and TRIUMPH-Outcomes, all still running (ClinicalTrials.gov).

Human Data

PubMed holds 200 records for retatrutide or LY3437943, 117 of them reviews (searched October 4, 2026). The trial reports are Phase 1 studies, two Phase 2 trials with their substudies, and three Phase 3 trials with 4,028 participants in all (Jastreboff et al., 2026; Bellido et al., 2026; Bajaj et al., 2026). Lilly has announced results from two more Phase 3 trials, with 2,394 participants, that are not yet published (Eli Lilly, December 11, 2025; Eli Lilly, July 23, 2026). Lilly sponsored all of them (ClinicalTrials.gov).

• Phase 1 single ascending dose (Coskun et al., 2022) — Safety and tolerability similar to other incretins; pharmacokinetics supported once-weekly dosing, and body weight stayed lower up to day 43 after one dose.
• Phase 1b T2D (NCT04143802; Urva et al., 2022) — 12-week multiple ascending dose trial in 72 adults with type 2 diabetes, with placebo and dulaglutide 1.5 mg for comparison: the group taken to 12 mg in steps lost 8.96 kg more than placebo, HbA1c fell in the three highest-dose groups, and the half-life was about 6 days (Urva et al., 2022). A 2023 review called the comparison with dulaglutide not meaningful, since semaglutide is more potent, and asked for comparisons with semaglutide and tirzepatide (Doggrell, 2023).
• Phase 2 obesity (NCT04881760; Jastreboff et al., 2023) — 338 adults with obesity, or overweight with a weight-related condition, randomized 2:1:1:1:1:2:2 to six dose groups or placebo for 48 weeks: weight fell 8.7% (1 mg), 17.1% (4 mg), 22.8% (8 mg) and 24.2% (12 mg), against 2.1% on placebo, and 83% of those on 12 mg lost at least 15%. Gastrointestinal events were dose-related and mostly mild to moderate; heart rate rose with dose and peaked at 24 weeks (Jastreboff et al., 2023).
• Phase 2 T2D (NCT04867785; Rosenstock et al., 2023) — 281 adults with type 2 diabetes at 42 US centres, against placebo and dulaglutide 1.5 mg: at 24 weeks HbA1c fell by up to 2.02% (12 mg), against 0.01% on placebo and 1.41% on dulaglutide; at 36 weeks weight fell by up to 16.94%, against 3.00% and 2.02%. HbA1c fell significantly more than on dulaglutide only in the 8 mg slow-escalation and 12 mg groups; weight fell more at every dose from 4 mg up (Rosenstock et al., 2023).
• Phase 2 MASLD substudy (Sanyal et al., 2024) — 98 participants with fatty liver; liver fat on MRI fell by up to 82.4% at 24 weeks (Sanyal et al., 2024; details under What the Research Shows).
• Body composition substudy (Coskun et al., 2025) — 189 participants of the Phase 2 type 2 diabetes trial, 103 with scans at both ends: total fat mass fell by up to 26.1% at 36 weeks (8 mg), against 4.5% on placebo, and the share of weight lost as lean mass was similar to other obesity treatments (Coskun et al., 2025).
• TRIUMPH-1 (NCT05929066; Jastreboff et al., 2026) — Phase 3, 2,339 adults with obesity without diabetes, 4, 9 or 12 mg against placebo for 80 weeks: weight fell 17.6%, 23.7% and 25.0%, against 3.9% on placebo. In the 574 with knee osteoarthritis, WOMAC pain fell by 3.4, 3.9 and 4.1 points, against 2.5; in the 243 with obstructive sleep apnea, apnea-hypopnea events fell by 22.8, 34.3 and 32.1 an hour, against 9.6 (intention-to-treat estimates; Jastreboff et al., 2026). The most common adverse events were gastrointestinal (Jastreboff et al., 2026). Lilly reports that 532 participants with a BMI of 35 or more who finished the 80 weeks and tolerated their dose continued for 24 more weeks, and that those on 12 mg had lost 30.3% at 104 weeks (efficacy estimand; Eli Lilly, May 21, 2026).
• TRIUMPH-2 (NCT05929079; Bellido et al., 2026) — Phase 3, 1,152 adults with obesity and type 2 diabetes at 92 centres in eight countries, 80 weeks: weight fell 11.9% (4 mg), 16.8% (9 mg) and 18.8% (12 mg), against 5.1% on placebo; six participants on retatrutide and one on placebo died, and the investigators judged none of the deaths related to the study drug (Bellido et al., 2026). Lilly reports HbA1c falls of 1.4%, 1.6% and 1.5% from a baseline of 7.7%, against 0.2% on placebo (efficacy estimand; Eli Lilly, September 29, 2026).
• TRIUMPH-3 (NCT05882045; not yet published) — Phase 3, 1,949 adults with a BMI of 35 or more and established cardiovascular disease, with or without type 2 diabetes, randomized 1:1:2 to 9 mg, 12 mg or placebo for 80 weeks. Lilly reports weight falls of 21.6% and 22.6%, against 3.2% on placebo (efficacy estimand; Eli Lilly, July 23, 2026). Major cardiovascular events were fewer than Lilly anticipated in every group: 44 on retatrutide (both doses together) against 52 on placebo for a composite of death from any cause, heart attack, stroke, heart failure event or coronary revascularization (hazard ratio 0.82, 95% CI 0.55–1.22), and 27 against 23 for cardiovascular death, heart attack or stroke (hazard ratio 1.12, 0.64–1.96) (Eli Lilly, July 23, 2026); both intervals include 1, so neither result shows a clear difference from placebo. The trial’s sample size was set to detect weight loss (Giblin et al., 2026).
• TRIUMPH-4 (NCT05931367; not yet published) — Phase 3, 445 adults with obesity or overweight and knee osteoarthritis, 9 or 12 mg against placebo for 68 weeks. Lilly reports weight falls of 26.4% and 28.7%, against 2.1% on placebo, and WOMAC pain falls of 4.5 and 4.4 points from a baseline of 6.0, against 2.4 (efficacy estimand); by the treatment-regimen estimand, which counts people whether or not they kept taking the drug, weight fell 20.0% and 23.7%, against 4.6% (Eli Lilly, December 11, 2025).
• TRANSCEND-T2D-1 (NCT06354660; Bajaj et al., 2026) — Phase 3, 537 adults with type 2 diabetes managed by diet and exercise alone, at 48 sites in the USA, Mexico and India, 4, 9 or 12 mg against placebo for 40 weeks: HbA1c fell 1.69%, 1.86% and 1.94%, against 0.81% on placebo, and weight fell 11.5%, 13.9% and 15.3%, against 2.6%. Adverse events led 2–5% to stop retatrutide, against none on placebo; no severe hypoglycaemia was reported, and two deaths, both on 4 mg, were reported as unrelated to the study drug (Bajaj et al., 2026).
• TRANSCEND-CKD (NCT05936151) — Phase 2b, 146 adults with overweight or obesity and chronic kidney disease, randomized to retatrutide (up to 12 mg) or placebo, with measured kidney filtration at 24 weeks as the main result (Heerspink et al., 2026). The registry lists it as completed in October 2025; no results are published (PubMed, searched October 4, 2026).
• Registered, not yet reported — TRANSCEND-T2D-2, against semaglutide in type 2 diabetes, reached its primary completion in August 2026 (NCT06260722); TRANSCEND-T2D-3, in type 2 diabetes with moderate or severe kidney impairment, is due in October 2026 (NCT06297603), and TRIUMPH-5, against tirzepatide in obesity, in November 2026 (NCT06662383). The cardiovascular and kidney outcomes trial, in about 10,000 adults, is due in February 2029 (NCT06383390). Every registered trial still running is listed under Pipeline below.

The TRIUMPH trials tested knee osteoarthritis and sleep apnea inside the weight-loss trials, a basket design (Giblin et al., 2026). Lilly says the clinical data are now complete to support applications for obesity, obstructive sleep apnea and knee osteoarthritis pain, and plans to submit a Biologics License Application to the FDA in the first quarter of 2027 (Eli Lilly, August 5, 2026).

Pipeline

• Biologics License Application to FDA planned for Q1 2027 (Eli Lilly, September 29, 2026)
• Phase 3 TRANSCEND-T2D-2 vs semaglutide (type 2 diabetes; primary completion reached August 2026, results not yet reported) (NCT06260722)
• Phase 3 TRANSCEND-T2D-3 (type 2 diabetes with moderate or severe kidney impairment) (NCT06297603), primary completion est. Oct 2026
• Phase 3 TRIUMPH-5 vs tirzepatide (NCT06662383), primary completion est. Nov 2026
• Phase 3 TRIUMPH-8 (obesity or overweight without type 2 diabetes) (NCT07232719), primary completion est. Jul 2027
• Phase 3 TRIUMPH-7 (obesity or overweight with chronic low back pain) (NCT07035093), primary completion est. Sep 2027
• Phase 3 TRIUMPH-6 (keeping weight off) (NCT06859268), primary completion est. Apr 2028
• Phase 3 TRIUMPH-9 (dose-escalation schemes) (NCT07357415), primary completion est. Oct 2028
• Phase 3 TRIUMPH-Outcomes (cardiovascular and kidney outcomes) (NCT06383390), primary completion est. Feb 2029
• Phase 3 SYNERGY-Outcomes (liver outcomes in fatty liver disease; retatrutide and tirzepatide arms) (NCT07165028), primary completion est. Aug 2030
• Phase 1 study of insulin secretion and sensitivity in type 2 diabetes (NCT06982859), primary completion est. Jan 2027

Reconstitution & Storage

Retatrutide has no approved label, so no official storage or handling instructions exist. Research-chemical sellers list it as freeze-dried powder in vials, for research use only, to be mixed with bacteriostatic water. For a mixed vial, the arithmetic depends on the vial mass, the water volume and the dose; the 2 mg and 8 mg columns are trial doses (see Dosing).

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Side Effects & Risks

The investigators called the safety profile consistent with GLP-1 and GIP/GLP-1 drugs in the Phase 2 diabetes trial (Rosenstock et al., 2023), and consistent with drugs that act on the GLP-1 receptor in TRIUMPH-2 and TRANSCEND-T2D-1 (Bellido et al., 2026; Bajaj et al., 2026). Beyond the gastrointestinal effects, dysesthesia and low blood pressure came more often on retatrutide than on placebo (Bellido et al., 2026), and Lilly reports urinary tract infections separately (below).

• GI tolerability (dose-dependent) — Gastrointestinal events were the most common adverse events in the Phase 3 trials (Jastreboff et al., 2026; Bajaj et al., 2026). In TRIUMPH-2, diarrhoea came in 27%, 34% and 34% on 4, 9 and 12 mg, against 13% on placebo, and nausea in 14%, 21% and 28%, against 8% (Bellido et al., 2026). Lilly reports nausea in 28.6%, 38.4% and 42.4%, against 14.8%, and vomiting in 10.6%, 22.8% and 25.3%, against 4.8%, in TRIUMPH-1 (Eli Lilly, May 21, 2026), and, on 9 and 12 mg, nausea in 38.1% and 43.2%, against 10.7%, and vomiting in 20.4% and 20.9%, against none, in TRIUMPH-4 (Eli Lilly, December 11, 2025). In Phase 2, gastrointestinal events were dose-related and mostly mild to moderate (Jastreboff et al., 2023).
• Stopping treatment — Adverse events or death led 4%, 12% and 8% to stop on 4, 9 and 12 mg in TRIUMPH-2, against 5% on placebo (Bellido et al., 2026), and adverse events led 2–5% to stop in TRANSCEND-T2D-1, against none (Bajaj et al., 2026). Lilly reports 4.1%, 6.9% and 11.3%, against 4.9%, in TRIUMPH-1 (Eli Lilly, May 21, 2026); 9.8% and 13.5% on 9 and 12 mg, against 4.8%, in TRIUMPH-3 (Eli Lilly, July 23, 2026); and 12.2% and 18.2%, against 4.0%, in TRIUMPH-4, rates it says tracked baseline BMI and included people who stopped because they felt they had lost too much weight (Eli Lilly, December 11, 2025).
• Dysesthesia — Dysesthesia, abnormal sensations such as burning skin, came more often on retatrutide than on placebo in all five Phase 3 trials: in 4%, 6% and 7% on 4, 9 and 12 mg in TRIUMPH-2, against 1% (Bellido et al., 2026), and, by Lilly’s figures, in 5.1%, 12.3% and 12.5% against 0.9% in TRIUMPH-1, 6.4% and 6.4% against 1.3% in TRIUMPH-3, 8.8% and 20.9% against 0.7% in TRIUMPH-4, and 4.5%, 2.3% and 4.4% against none in TRANSCEND-T2D-1, most cases mild to moderate (Eli Lilly, May 21, 2026; Eli Lilly, July 23, 2026; Eli Lilly, December 11, 2025; Eli Lilly, March 19, 2026). A 2026 pharmacovigilance study found dysesthesia and burning sensations reported more often than expected with semaglutide, and says dysesthesia with drugs of this class appears to be dose-dependent (Laroche et al., 2026).
• Low blood pressure — Hypotension came in 1%, 5% and 6% on 4, 9 and 12 mg in TRIUMPH-2, against under 1% on placebo (Bellido et al., 2026).
• Urinary tract infections — Lilly reports them in 7.5%, 8.8% and 8.4% on 4, 9 and 12 mg, against 5.3% on placebo, in TRIUMPH-1 (Eli Lilly, May 21, 2026); in 0.7%, 1.5% and 2.9%, against none, in TRANSCEND-T2D-1 (Eli Lilly, June 6, 2026); in 6.1% and 7.0% on 9 and 12 mg, against 5.3%, in TRIUMPH-3; and in 3.8%, 6.3% and 8.0%, against 6.6%, in TRIUMPH-2, where only 12 mg was above placebo (Eli Lilly, July 23, 2026). Lilly describes most as mild to moderate.
• Heart rate — In the Phase 2 obesity trial, heart rate rose with dose, peaked at 24 weeks and declined thereafter (Jastreboff et al., 2023).
• Major cardiovascular events — In TRIUMPH-3, in adults with established cardiovascular disease, Lilly reports hazard ratios of 0.82 (95% CI 0.55–1.22) and 1.12 (0.64–1.96) for two composites of major cardiovascular events, from 96 and 50 events in all (Eli Lilly, July 23, 2026); both intervals include 1, so neither result shows a clear difference from placebo. The trial designed to test heart and kidney outcomes is due in February 2029 (NCT06383390).
• Deaths in the trials — TRIUMPH-2 recorded six deaths on retatrutide and one on placebo, all judged unrelated to the study drug by the investigators (Bellido et al., 2026); TRANSCEND-T2D-1 recorded two, both on 4 mg, reported as unrelated (Bajaj et al., 2026).
• Low blood sugar — No severe hypoglycaemia was reported in TRANSCEND-T2D-1, where retatrutide was given without other diabetes drugs (Bajaj et al., 2026).
• Gallbladder events — Acute gallbladder disease is a listed warning on the label of tirzepatide (Zepbound), Lilly’s approved GIP and GLP-1 drug (Zepbound label).
• Pancreatitis — Acute pancreatitis is a listed warning on the Zepbound label (Zepbound label). TRIUMPH-1 excluded anyone who had had pancreatitis (ClinicalTrials.gov NCT05929066).
• MTC / thyroid C-cell (class boxed warning) — The Zepbound label carries a boxed warning: tirzepatide caused thyroid C-cell tumors in rats, whether it does in people is unknown, and a personal or family history of medullary thyroid carcinoma or MEN 2 is a contraindication (Zepbound label). TRIUMPH-1 excluded people with that history (ClinicalTrials.gov NCT05929066).
• Pregnancy and lactation — No published data. The Zepbound label says to stop tirzepatide when a pregnancy is recognized, because weight loss offers no benefit in pregnancy and may harm the fetus (Zepbound label).
• Purity and sourcing (gray market) — Outside the trials, retatrutide is sold as a research chemical, unregulated for quality. Three vials sold as retatrutide in Australia, each labelled 10 mg, held 5.13 mg, 16.5 mg and 19.0 mg; sterility and endotoxin were not tested (Piatkowski et al., 2026). FDA says products sold “for research purposes” are of unknown quality and may be harmful (FDA, October 1, 2026).
• Use outside the trials — A 2026 case report describes a man with type 1 diabetes who needed intravenous insulin and fluids for vomiting, diarrhoea, ketones up to 4.3 mmol/L and acute kidney injury shortly after using a product bought online as retatrutide; his partner, who took the same product, also had gut symptoms, both had eaten food that could have carried an infection, and Shigella grew from his stool (Branine, 2026). The author says causation cannot be established, but that the timing, his partner’s similar symptoms and retatrutide’s known gut side effects suggest it may have added to how severe the illness was, or to the metabolic effects of the infection (Branine, 2026).
• UK Yellow Card reports — A BMJ fact check of 9 July 2026 reports 77 reports of suspected side effects of retatrutide to the MHRA’s Yellow Card scheme, 59 of them serious, and one death, of a man in his 30s, reported in 2025 by a healthcare professional. It points out that a Yellow Card report records a suspicion and does not establish that the drug caused what happened, and that retatrutide cannot be prescribed in the UK, so the people in these reports got it on the black market or took it in a trial (Mahase, 2026). The fact check is behind BMJ’s paywall; what was read for this page is set out in its reference.
• Drug interactions — Retatrutide delays gastric emptying (Urva et al., 2023). For tirzepatide, which also does, the Zepbound label says the delay can affect the absorption of oral medicines, names narrow-therapeutic-index drugs such as warfarin, and lists a higher risk of low blood sugar with insulin or insulin secretagogues (Zepbound label).
• WADA status — Not named on the Prohibited List, but prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).

Bloodwork & Monitoring

No label or guideline sets monitoring for retatrutide, which is investigational. Besides weight, TRIUMPH-1 measured waist, blood pressure, triglycerides, non-HDL cholesterol, fasting insulin, hsCRP, HbA1c and kidney function (eGFR) over 80 weeks (ClinicalTrials.gov NCT05929066), and the Phase 2 obesity trial tracked heart rate (Jastreboff et al., 2023).

Commonly Stacked With

ClinicalTrials.gov lists no trial of retatrutide with any of these (October 4, 2026). Users and clinicians describe the first three pairings; the one with cagrilintide has been tested in obese male rats (Petersen et al., 2026).

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Legal Status

Related Compounds

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References

1. Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PMID: 37366315. DOI: 10.1056/NEJMoa2301972.
2. Rosenstock J, Frías JP, Jastreboff AM, et al. 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. 2023;402(10401):529-544. PMID: 37385280.
3. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037-2048. PMID: 38858523.
4. Coskun T, Urva S, Roell WC, 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):1234-1247.e9. PMID: 35985340.
5. Urva S, Coskun T, Loh MT, 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):1869-1881. PMID: 36354040.
6. Urva S, O’Farrell L, Du Y, Loh MT, Hemmingway A, Qu H, Alsina-Fernandez J, Haupt A, Milicevic Z, Coskun T. The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes Obes Metab. 2023;25(9):2784-2788. PMID: 37311727.
7. Coskun T, Wu Q, Schloot NC, 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):674-684. PMID: 40609566.
8. Doggrell SA. 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. 2023;32(5):355-359. PMID: 37086147.
9. Giblin K, Kaplan LM, Somers VK, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab. 2026;28(1):83-93. PMID: 41090431. DOI: 10.1111/dom.70209.
10. 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. PMID: 35658024. (Comparator reference.)
11. 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. PMID: 33567185. (Comparator reference.)
12. 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. PMID: 37952131. (Comparator reference.)
13. ClinicalTrials.gov. A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (TRIUMPH-1). NCT05929066. Completed; primary completion April 6, 2026. Read October 4, 2026.
14. ClinicalTrials.gov. A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight (TRIUMPH-2). NCT05929079. Completed; primary completion June 16, 2026. Read October 4, 2026.
15. ClinicalTrials.gov. A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease (TRIUMPH-3). NCT05882045. Completed; primary completion April 16, 2026. Read October 4, 2026.
16. ClinicalTrials.gov. A Study of Retatrutide (LY3437943) Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee (TRIUMPH-4). NCT05931367. Completed; primary completion November 14, 2025. Read October 4, 2026.
17. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Press release, December 11, 2025 (PR Newswire). prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-weight-loss-of-up-to-an-average-of-71-2-lbs-along-with-substantial-relief-from-osteoarthritis-pain-in-first-successful-phase-3-trial-302638804.html. Read October 4, 2026.
18. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download. Read October 4, 2026.
19. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.
20. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). N Engl J Med. 2026 (published online September 29, 2026). PMID: 42814954. DOI: 10.1056/NEJMoa2604169.
21. Bellido V, le Roux CW, Ekinci EI, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026 (published online September 29, 2026). PMID: 42810372. DOI: 10.1016/S0140-6736(26)01861-1.
22. Eli Lilly and Company. Zepbound (tirzepatide) injection, prescribing information. DailyMed set ID 487cd7e7-434c-4925-99fa-aa80b1cc776b (label version 40, effective August 28, 2026). dailymed.nlm.nih.gov. Read through openFDA, October 4, 2026.
23. Bajaj HS, Welch M, Shah P, Luna E, Jaouimaa FZ, Liu B, Liu R, Chen Y, Patel H, Bartee A. 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):2402-2413. PMID: 42250575. DOI: 10.1016/S0140-6736(26)00967-0.
24. Heerspink HJL, van Raalte DH, Bjornstad P, Bunck MC, Wu P, Tunali I, Milicevic Z, Koeneman L. Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease. Nephrol Dial Transplant. 2026;41(6):1058-1068. PMID: 41160422. DOI: 10.1093/ndt/gfaf230.
25. Petersen J, Merrild C, Holm SK, et al. Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats. Nat Metab. 2026. PMID: 42744908. DOI: 10.1038/s42255-026-01603-y.
26. Piatkowski T, Craven A, Cornell S, Ferris J. Composition and Labelling Accuracy of Products Sold as Retatrutide in Australia. Drug Alcohol Rev. 2026;45(6):e70231. PMID: 42559975. DOI: 10.1111/dar.70231.
27. Branine N. Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis. Cureus. 2026;18(8):e115260. PMID: 42669023. DOI: 10.7759/cureus.115260.
28. Laroche ML, Géniaux H, Jardou M. Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review. Eur J Clin Pharmacol. 2026;82(6):154. PMID: 42168638. DOI: 10.1007/s00228-026-04079-7.
29. Ruotolo G, Harris C, Lin Y, et al. Retatrutide-Associated Improvements in Cardiovascular Risk Biomarkers in Adults With Obesity With or Without Type 2 Diabetes. Diabetes Obes Metab. 2026. PMID: 42608321. DOI: 10.1111/dom.71200.
30. Elmendorf AJ, Yousefian M, Kim IM, Hardaway JA, Habegger K, Flak JN. IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes. Pharmacol Res. 2026;223:108077. PMID: 41478576. DOI: 10.1016/j.phrs.2025.108077.
31. Moiz A, Filion KB, Samuels AE, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes: An Updated Systematic Review. Ann Intern Med. 2026. PMID: 42673585. DOI: 10.7326/ANNALS-25-05519.
32. World Health Organization (WHO). International Nonproprietary Names for Pharmaceutical Substances (INN): Proposed INN List 128, retatrutide (chemical name, sequence of 39 residues with modified residues, formula C221H342N46O68). WHO Drug Information. 2022;36(4):1051. cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl128.pdf. Read October 4, 2026.
33. KEGG DRUG. Entry D12430, Retatrutide (USAN): formula C221H342N46O68, molecular weight 4731.34. kegg.jp/entry/D12430. Read October 4, 2026.
34. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes. Press release, March 19, 2026 (PR Newswire). prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-demonstrated-significant-reductions-in-a1c-and-weight-in-first-phase-3-trial-for-treatment-of-type-2-diabetes-302718589.html. Read October 4, 2026.
35. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Press release, May 21, 2026 (PR Newswire). prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html. Read October 4, 2026.
36. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea, demonstrating its remarkable potential to treat obesity and its complications. Press release, June 6, 2026 (PR Newswire). prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-drove-substantial-improvements-in-weight-a1c-knee-osteoarthritis-pain-and-obstructive-sleep-apnea-demonstrating-its-remarkable-potential-to-treat-obesity-and-its-complications-302793169.html. Read October 4, 2026.
37. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Press release, July 23, 2026 (PR Newswire). prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html. Read October 4, 2026.
38. Eli Lilly and Company. Lilly reports second-quarter 2026 financial results, raises full-year guidance, and highlights continued growth and pipeline progress. Press release, August 5, 2026 (PR Newswire; the same text is Exhibit 99.1 to Lilly’s Form 8-K of that day, sec.gov/Archives/edgar/data/59478/000005947826000077/q226lillysalesandearningsp.htm). prnewswire.com/news-releases/lilly-reports-second-quarter-2026-financial-results-raises-full-year-guidance-and-highlights-continued-growth-and-pipeline-progress-302843165.html. Read October 4, 2026.
39. Eli Lilly and Company. Lilly calls on online platforms, payment companies and regulators to shut down the illegal retatrutide black market. Press release, August 12, 2026 (PR Newswire). prnewswire.com/news-releases/lilly-calls-on-online-platforms-payment-companies-and-regulators-to-shut-down-the-illegal-retatrutide-black-market-302849551.html. Read October 4, 2026.
40. Eli Lilly and Company. Lilly to present new data on Foundayo, retatrutide, and eloraTZP at EASD 2026, as it strives to change the course of cardiometabolic health. Press release, September 15, 2026 (PR Newswire). prnewswire.com/news-releases/lilly-to-present-new-data-on-foundayo-retatrutide-and-eloratzp-at-easd-2026-as-it-strives-to-change-the-course-of-cardiometabolic-health-302878341.html. Read October 4, 2026.
41. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. Press release, September 29, 2026 (PR Newswire). prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-substantial-weight-loss-and-a1c-reduction-underscoring-its-potential-promise-for-people-with-obesity-and-type-2-diabetes-302891798.html. Read October 4, 2026.
42. FDA. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. Content current as of October 1, 2026. fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss. Read October 4, 2026.
43. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated March 21, 2025. fda.gov/media/94164/download. Read October 4, 2026.
44. Code of Federal Regulations. 21 CFR 216.23, Bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act. ecfr.gov. Read October 4, 2026.
45. FDA. Drugs@FDA through openFDA (api.fda.gov/drug/drugsfda.json), search for retatrutide, October 4, 2026 (no records); National Drug Code Directory, retatrutide listings (api.fda.gov/drug/ndc.json, data of October 2, 2026: bulk-ingredient powder from eight labelers), and “National Drug Code Directory” (FDA NDC Directory, 2026: content current as of March 4, 2026), fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory. European Medicines Agency. Medicines data table (ema.europa.eu, medicines-output-medicines_json-report), searched for retatrutide, October 4, 2026 (no entry). Read October 4, 2026.
46. ClinicalTrials.gov. Pre-approval Expanded Access of Retatrutide (LY3437943). NCT07629401. Expanded access, available; first posted June 5, 2026. Read October 4, 2026.
47. ClinicalTrials.gov. A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (TRIUMPH-5). NCT06662383. Active, not recruiting; primary completion estimated November 2026. Read October 4, 2026.
48. ClinicalTrials.gov. The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes). NCT06383390. Active, not recruiting; about 10,000 participants; primary completion estimated February 2029. Read October 4, 2026.
49. ClinicalTrials.gov. Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2). NCT06260722. Active, not recruiting; primary completion August 27, 2026. Read October 4, 2026.
50. ClinicalTrials.gov. Effect of Retatrutide Compared With Placebo in Participants With Type 2 Diabetes and Moderate or Severe Renal Impairment, With Inadequate Glycemic Control on Basal Insulin, With or Without Metformin and/or SGLT2 Inhibitor (TRANSCEND-T2D-3). NCT06297603. Active, not recruiting; primary completion estimated October 2026. Read October 4, 2026.
51. ClinicalTrials.gov. Other registered retatrutide trials, read October 4, 2026: TRANSCEND-CKD, Phase 2b in chronic kidney disease (NCT05936151, completed October 2025, no results posted); a master protocol of retatrutide and tirzepatide in fatty liver disease, SYNERGY-Outcomes (NCT07165028, recruiting); TRIUMPH-6, weight maintenance (NCT06859268); TRIUMPH-7, chronic low back pain (NCT07035093); TRIUMPH-8 (NCT07232719); TRIUMPH-9, dose-escalation schemes (NCT07357415); and a Phase 1 study of insulin secretion and sensitivity (NCT06982859), all active, not recruiting.
52. Searches of October 4, 2026: PubMed, “retatrutide OR LY3437943” (200 records; 117 tagged review; 195 for “retatrutide” alone), and retatrutide with osteoarthritis, sleep apnea, kidney, randomized controlled trial and TRANSCEND (no TRIUMPH-3 or TRIUMPH-4 paper); Europe PMC, retatrutide 2026 outside MEDLINE (12 records, including three preprints, not used); ClinicalTrials.gov, “retatrutide” and “LY3437943” (34 records each, 35 in all; NCT07467447, listed under the sponsor “Hudson Biotech”, repeats the official title and protocol code of Lilly’s Phase 2 trial (NCT04881760) and is not cited; NCT07226947 is an exercise study in people on any incretin); PR Newswire’s Eli Lilly newsroom, December 2025 to October 2, 2026 (12 releases on retatrutide or with retatrutide news, read in full); SEC EDGAR full-text search, “retatrutide” in Form 8-K filings; openFDA Drugs@FDA, labels and NDC; DailyMed; the European Medicines Agency’s medicines data; WHO INN proposed lists 126–128; KEGG DRUG.
53. Mahase E. Retatrutide fact check: Has a man died after taking the unapproved weight loss jab? BMJ. 2026;394:e100245. PMID: 42425580. DOI: 10.1136/bmj-2026-100245. (Behind BMJ’s paywall: its PubMed record was read on October 12, 2026; the figures and points given on this page are the fact check’s, as G read them in it.)

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