For research purposes only. Not for human use. Retatrutide is an investigational compound that has not been approved by any regulatory agency. Nothing on this page is medical advice or a protocol for administration.
What Retatrutide Is
Retatrutide (Eli Lilly code LY3437943) is a single synthetic peptide engineered to activate three receptors at once: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. It is administered once weekly in clinical trials and is the most advanced "triple agonist" in the incretin drug class, sitting one generation past semaglutide (GLP-1 only) and tirzepatide (GIP/GLP-1).
The design rationale, published by Coskun and colleagues in Cell Metabolism in 2022, was to combine the appetite-suppressing effects of GIP and GLP-1 receptor activity with the energy-expenditure effects of glucagon receptor activity. In vitro, LY3437943 showed balanced glucagon and GLP-1 receptor activity but more GIP receptor activity; in obese mice, weight loss was augmented by adding glucagon-receptor-driven increases in energy expenditure to the calorie-intake reduction driven by the other two receptors (Coskun et al., 2022). The same paper reported a phase 1 single-ascending-dose study in which the pharmacokinetic profile supported once-weekly dosing and a reduction in body weight persisted to day 43 after a single dose.
For researchers, retatrutide is interesting less as a product than as a test of a hypothesis: that deliberately adding glucagon receptor agonism, long avoided in obesity pharmacology because glucagon raises blood glucose, produces more weight and liver-fat reduction than dual agonism without losing glycaemic control. The phase 2 and early phase 3 data below are the evidence for and against that hypothesis.
Phase 2 Obesity Trial (NEJM, 2023)
The pivotal phase 2 obesity study enrolled 338 adults with a BMI of 30 or higher (or 27 to 30 with a weight-related condition) and randomised them to placebo or to one of several once-weekly retatrutide arms for 48 weeks. The primary endpoint was percentage change in body weight at 24 weeks (Jastreboff et al., 2023).
At 48 weeks, the least-squares mean weight change was −8.7% in the lowest arm, −17.1% in the combined 4 mg arms, −22.8% in the combined 8 mg arms and −24.2% in the 12 mg arm, against −2.1% with placebo. In the two highest arms, every participant lost at least 5% of body weight, 91–93% lost at least 10%, and 75–83% lost at least 15%. The most common adverse events were gastrointestinal, dose-related, mostly mild to moderate, and partly mitigated by a lower starting dose. Dose-dependent increases in heart rate peaked at 24 weeks and declined afterwards.
The weight-loss curves had not plateaued at 48 weeks, so the trial does not establish a maximum effect. The −24.2% figure is a least-squares mean from a 48-week phase 2 study of 338 people; it is not a phase 3 result and should not be quoted as one.
Phase 2 MASLD Sub-study (Nature Medicine, 2024)
A pre-specified sub-study of the same trial followed 98 participants who had metabolic dysfunction-associated steatotic liver disease with at least 10% liver fat at baseline. The primary objective was the relative change in liver fat at 24 weeks measured by MRI-proton density fat fraction (Sanyal et al., 2024).
Mean relative liver-fat change at 24 weeks was −42.9%, −57.0%, −81.4% and −82.4% across the four ascending arms, against +0.3% with placebo. Normal liver fat (below 5%) was reached by 27%, 52%, 79% and 86% of participants in those arms and by none on placebo. Liver-fat reductions tracked changes in body weight, abdominal fat and markers of insulin sensitivity and lipid metabolism.
The glucagon receptor is the mechanistic candidate for why the liver-fat effect is larger than the weight-loss effect alone would predict: hepatic glucagon signalling increases fatty-acid oxidation and suppresses lipogenesis. The sub-study was not designed to separate that direct hepatic effect from the indirect effect of losing a quarter of body weight, so the causal split remains an open research question.
Type 2 Diabetes: Phase 2 and the First Phase 3 Readout
The phase 2 type 2 diabetes trial randomised 281 adults with HbA1c of 7.0–10.5% to placebo, dulaglutide 1.5 mg, or retatrutide across a range of maintenance doses for 36 weeks (Rosenstock et al., 2023). At 24 weeks, HbA1c fell by roughly 0.4 percentage points in the lowest arm and by about 2.0 points in the 8 mg and 12 mg arms; body weight fell substantially in parallel, with a safety profile the authors described as consistent with GLP-1 and GIP/GLP-1 receptor agonists. These data set the doses for the phase 3 programme.
A body-composition sub-study of that trial (189 participants, DXA scans at baseline and week 36) found total fat mass reductions of 15.2%, 26.1% and 23.2% in the pooled 4 mg, pooled 8 mg and 12 mg arms, against 2.6% with dulaglutide and 4.5% with placebo. The proportion of lean mass lost relative to total weight lost was similar to other obesity treatments, which the authors framed as reassurance that greater total weight loss did not come with disproportionate lean-mass loss (Lancet Diabetes & Endocrinology, 2025).
The first phase 3 result, TRANSCEND-T2D-1, was published in The Lancet in 2026. It enrolled 537 adults with type 2 diabetes inadequately controlled by diet and exercise and randomised them to placebo or retatrutide 4 mg, 9 mg or 12 mg for 40 weeks. HbA1c fell by 1.69, 1.86 and 1.94 percentage points versus 0.81 with placebo; body weight fell by 11.5%, 13.9% and 15.3% versus 2.6%. Discontinuations due to adverse events were 2–5% with retatrutide and 0% with placebo, no severe hypoglycaemia was reported, and the two deaths in the study (both in the 4 mg group) were judged unrelated to the drug (Bajaj et al., 2026).
The Rest of the Phase 3 Programme
The TRIUMPH programme evaluates retatrutide in obesity using a basket design: four phase 3 trials in more than 5,800 participants, with obstructive sleep apnoea and knee osteoarthritis protocols nested inside the weight-management trials, one weight-management trial in people with cardiovascular disease, and a stand-alone knee osteoarthritis trial. Primary endpoints are percentage weight change, change in the apnoea-hypopnoea index, and change in the WOMAC pain subscale respectively (Diabetes, Obesity and Metabolism, 2026). A separate kidney trial, TRANSCEND-CKD, has published its design and baseline characteristics (Nephrology Dialysis Transplantation, 2026).
A post hoc analysis of the two phase 2 studies looked at kidney parameters. In participants with type 2 diabetes, the 12 mg dose was associated with a 37% reduction in urine albumin-to-creatinine ratio versus placebo at 36 weeks with no change in eGFR. In participants with obesity but not diabetes, the 8 mg and 12 mg doses reduced albuminuria by 28–32% and increased creatinine-derived eGFR by 5–9 ml/min per 1.73 m². Because most participants had normal albuminuria at baseline, the absolute reductions were modest (Kidney International Reports, 2025).
Safety Signals Reported So Far
Across the published trials the adverse-event profile is the one expected from the incretin class: nausea, vomiting, diarrhoea and constipation, dose-related, most frequent during escalation, and reduced by starting lower. Two signals are specific enough to track separately.
Heart rate rose in a dose-dependent way in the phase 2 obesity trial, peaking at 24 weeks and declining thereafter. Glucagon receptor agonism and GLP-1 receptor agonism both raise heart rate, and whether the peak-then-decline pattern holds over years is one of the questions the cardiovascular-population TRIUMPH trial is designed to answer.
A 2024 systematic review and meta-analysis of the three placebo-controlled randomised trials available at that time (640 participants, 510 on retatrutide) reported a pooled weight difference of −10.66 kg versus placebo, with an increase in non-severe gastrointestinal and hypersensitivity adverse events and no signal for severe hypoglycaemia (Metabolism Open, 2024). The authors noted the evidence base was small and phase 3 data were needed for long-term safety.
Nothing published so far establishes long-term safety, and the trials all used pharmaceutical-grade material manufactured under GMP with validated potency. None of that applies to research-grade retatrutide sold online, which brings its own questions of identity, purity and endotoxin content that no clinical trial addresses.
How Retatrutide Compares to Semaglutide and Tirzepatide
No head-to-head trial has been published. The comparisons circulating online place the 48-week phase 2 retatrutide result (−24.2%) next to the 68-week STEP 1 semaglutide result (−14.9%) and the tirzepatide phase 3 results; those trials had different durations, populations and analysis methods, so the gap between them is suggestive rather than measured. The body-composition sub-study is the only place retatrutide has been compared directly with another agent (dulaglutide) on a mechanistic endpoint.
For a structured comparison of the three molecules see retatrutide vs tirzepatide, the semaglutide research overview and the GLP-1 receptor agonist overview. The half-life tool models the once-weekly exposure profile shared across the class.
Platform Market Data: Retatrutide Listings
The figures below are computed from the Peptides.SO listings table (10,922 priced listings across 119 suppliers, prices checked 24–25 September 2026). They describe the research-chemical market, not pharmaceutical supply, and say nothing about what is in any given vial.
| Product row | Listings | Suppliers | Median list price | Interquartile range | Median at sale price |
|---|---|---|---|---|---|
| Retatrutide (all sizes) | 58 | 27 | $169.00 | $112.50 – $317.25 | $160.50 |
| Retatrutide 10 mg | 13 | 10 | $149.00 | — | — |
| Retatrutide 20 mg | 5 | 4 | $216.00 | — | — |
The full range on the main row runs from $45 to $1,780; entries above roughly $500 are multi-vial kits or 60–120 mg bulk vials stored under the same product row, so the median is a better guide than the spread. Compared with the platform median for semaglutide ($119.99, 51 listings, 23 suppliers), research-grade retatrutide is priced about 40% higher for a compound with no approved reference standard.
Live prices, supplier count and stock status are on the retatrutide product page. Use the cost calculator to convert list prices to cost per milligram across vial sizes and the supplier checklist before purchasing. Because no pharmacopoeial monograph exists, a supplier's certificate of analysis should show HPLC purity, mass spectrometry confirming the expected molecular mass, and an endotoxin result; a certificate missing any of those is not a certificate.
Handling Notes for Laboratory Use
Retatrutide is a lipidated peptide supplied as a lyophilised powder. Like other acylated incretin analogues it is sensitive to repeated freeze-thaw cycles, agitation after reconstitution and light exposure. Unopened lyophilised vials are generally stored frozen; reconstituted material is stored refrigerated and used within the window the supplier's stability data supports. Laboratories reconstituting for in vitro or analytical work can use the peptide calculator to compute concentrations from vial mass and diluent volume. These are handling notes for laboratory material, not administration guidance.
Frequently Asked Questions
Is retatrutide approved anywhere?
No. As of September 2026 it is in phase 3 trials (TRIUMPH, TRANSCEND, and liver and kidney programmes). The first phase 3 publication, TRANSCEND-T2D-1, appeared in The Lancet in 2026. Any product sold as retatrutide is unapproved research material.
Why add glucagon agonism if glucagon raises blood glucose?
The hypothesis is that GIP and GLP-1 receptor activity offsets glucagon's glucose-raising effect while glucagon contributes energy expenditure and hepatic fat oxidation. The phase 2 diabetes trial and TRANSCEND-T2D-1 both showed HbA1c falling rather than rising, which supports the offset in the doses studied.
How large was the liver-fat effect?
In the MASLD sub-study, the two highest arms reduced liver fat by 81–82% at 24 weeks and 79–86% of participants reached normal liver fat, compared with 0% on placebo. Participants had at least 10% liver fat at baseline.
Does retatrutide cause more lean-mass loss than other agents?
The DXA sub-study found the proportion of weight lost as lean mass was similar to other obesity treatments; total fat-mass reduction was 23–26% in the higher arms versus 2.6% with dulaglutide.
What is the heart-rate signal?
Dose-dependent heart-rate increases were reported in phase 2, peaking around week 24 and declining afterwards. Longer trials, including one in a cardiovascular-disease population, are needed to characterise it.
How does research-grade retatrutide differ from trial material?
Trial material is GMP-manufactured with validated identity, potency and impurity profiles. Research-grade material has whatever the supplier's certificate of analysis shows, and often less. That difference, not the molecule, is the main source of risk in the research market.
References
1. Coskun T, 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. PMID 35985340
2. Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023. PMID 37366315
3. Sanyal AJ, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024. PMID 38858523
4. Rosenstock J, 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. PMID 37385280
5. Coskun T, 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. PMID 40609566
6. Bajaj HS, 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. PMID 42250575
7. Giblin K, 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. PMID 41090431
8. Heerspink HJL, et al. Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease. Nephrol Dial Transplant. 2026. PMID 41160422
9. Heerspink HJL, et al. The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity. Kidney Int Rep. 2025. PMID 40630318
10. Pasqualotto E, et al. Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials. Metabol Open. 2024. PMID 39318607
Research Disclaimer
Retatrutide is an investigational compound available to laboratories for research use only. It is not approved for human or veterinary use, and this article does not describe or endorse any administration to people or animals. Trial doses are quoted only to identify the published results they belong to. Anyone considering GLP-1-class therapy should speak to a licensed clinician about approved medicines.