Research index

Neutral one-line summaries with a link to each primary source. Null and negative findings are listed alongside positive ones.

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept — The originating Eli Lilly paper. It characterises LY3437943 as a single peptide with agonist activity at the glucagon, GIP and GLP-1 receptors, reports balanced GCGR and GLP-1R activity with more GIPR activity in vitro, and attributes the additional body-weight effect seen in obese mice to GCGR-mediated increases in energy expenditure on top of GIPR- and GLP-1R-driven reduction in calorie intake. In a phase 1 single ascending-dose study the authors report a safety and tolerability profile similar to other incretins, a pharmacokinetic profile supporting once-weekly dosing, and a reduction in body weight persisting to day 43 after a single dose. source
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 — The first human pharmacokinetic characterisation, in 72 participants with type 2 diabetes over 12 weeks (NCT04143802). Pharmacokinetics were dose proportional and the half-life was approximately 6 days. Treatment- emergent adverse events were reported by 63% of those receiving LY3437943, against 54% on placebo, with gastrointestinal disorders most frequent; 29 of the 72 participants discontinued the study prematurely. The authors describe the safety profile as acceptable in an early phase study and the pharmacokinetics as suggesting suitability for once-weekly dosing. source
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 — A phase 2 trial in 281 adults with type 2 diabetes across 42 US centres (NCT04867785), with placebo and dulaglutide as comparators. The primary endpoint was change in HbA1c from baseline to 24 weeks. 237 participants (84%) completed the study and 222 (79%) completed study treatment. The trial was not designed or powered for clinical outcomes, and its comparator was dulaglutide rather than the most potent available alternative — a limitation raised in the contemporaneous commentary literature. source
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial — A phase 2 double-blind randomised placebo-controlled trial in 338 adults (NCT04881760), running 48 weeks. The reported least-squares mean percentage change in body weight at 48 weeks was -8.7%, -17.1%, -22.8% and -24.2% across the ascending retatrutide groups against -2.1% with placebo. The most common adverse events in the retatrutide groups were gastrointestinal, dose-related, mostly mild to moderate, and partially mitigated by a lower starting dose. The authors record dose-dependent increases in heart rate that peaked at 24 weeks and declined thereafter. source
Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials — The design paper for the registrational programme, authored largely by the sponsor. TRIUMPH comprises four phase 3 multicentre randomised double-blind studies of weekly subcutaneous retatrutide against placebo, alongside diet and physical activity, in over 5800 participants, using a basket design that evaluates obesity together with obstructive sleep apnea and knee osteoarthritis. It is a protocol description, not a results paper, and reports no outcomes. source
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 — The first completed phase 3 trial of retatrutide to be published in full. 537 adults at 48 sites in the USA, Mexico and India were randomised over 40 weeks (NCT06354660). Mean change in HbA1c from baseline was -1.69%, -1.86% and -1.94% across the three ascending retatrutide groups against -0.81% with placebo; mean percentage change in body weight was -11.5%, -13.9% and -15.3% against -2.6% with placebo. Adverse events were most frequently mild to moderate gastrointestinal events; discontinuations of the study intervention owing to adverse events were 2-5% with retatrutide and 0% with placebo; no severe hypoglycaemia was reported. Two deaths occurred, both in the lowest-dose group, and both were reported as unrelated to the study drug. Funded by Eli Lilly and Company. source
Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease — A phase 2b mechanistic study in 146 randomised adults with overweight or obesity and chronic kidney disease (NCT05936151), measuring change in glomerular filtration rate by iohexol clearance to week 24. This is a design and baseline-characteristics paper; it reports who was enrolled, not what happened to them. The authors state its purpose is to inform the ongoing cardio-kidney outcome trial TRIUMPH-Outcomes (NCT06383390). source
Composition and Labelling Accuracy of Products Sold as Retatrutide in Australia — An independent laboratory analysis of three products sold as retatrutide and labelled as containing 10 mg each, submitted anonymously to a community drug-checking service and analysed by an accredited laboratory. All three contained retatrutide by molecular weight. Measured content was 5.13 mg, 16.5 mg and 19.0 mg — 51.3%, 165.0% and 190.0% of the labelled amount. No arsenic, cadmium, chromium, nickel or mercury was found above quantitation limits; lead, copper and zinc were detected at levels the authors interpreted as substantially below toxicologically relevant thresholds. The authors note only three samples were analysed and that the findings may not reflect the broader illicit peptide market. source
Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis — A single case report from an acute medicine unit. A man in his mid-30s with longstanding type 1 diabetes presented with severe vomiting, diarrhoea, hyperglycaemia, ketonaemia and acute kidney injury shortly after self-administering an online-purchased product marketed as retatrutide; his partner, who took the same preparation, also developed gastrointestinal symptoms. Stool culture grew Shigella flexneri, and the author states causation cannot be established. Recorded here as a documented presentation following non-pharmaceutical supply, not as evidence of an effect. source
Detection and Excretion Profile of Retatrutide in Human Plasma and Urine by LC-HRMS - Implications for Antidoping Analysis — An anti-doping laboratory validated an LC-HRMS method to World Anti-Doping Agency criteria, reaching limits of detection of 6.14 ng/mL in plasma and 2.44 ng/mL in urine. In four self-administering users, neither intact retatrutide nor metabolite-derived signals were detected in urine at any timepoint despite multiple extraction strategies, while the plasma detection window extended to approximately 56 days after the first dose. Analytical chemistry for doping control, not a study of any effect in a person. source

What the research does not show

The central limitation of this compound is not weak evidence. It is the gap between the evidence and the supply. Retatrutide has completed phase 3 trials in thousands of participants, and it is simultaneously approved nowhere, prohibited in compounding by FDA, and available to consumers only through channels that no regulator oversees. Strong trial results are not a lawful route to the substance and say nothing about material obtained outside one. source
Every clinical figure on this page was produced with material manufactured by the sponsor to pharmaceutical standards, administered on a fixed escalation schedule under medical supervision, with protocol criteria for stopping. None of those conditions holds outside a trial, and the trials measured nothing about material bought elsewhere. source
The identity and content of non-pharmaceutical supply is not characterised. The only independent analysis located tested three products sold as retatrutide in Australia and found content ranging from 51.3% to 190.0% of the labelled amount. Its authors state plainly that only three samples were analysed and that the findings may not reflect the broader illicit peptide market. A three-sample study is the entire published evidence base on what is actually in these products. source
Detailed results for most of the phase 3 programme have not been published or peer reviewed. As of this entry, of the completed phase 3 studies only TRANSCEND-T2D-1 has appeared as a full paper. TRIUMPH-1, TRIUMPH-2, TRIUMPH-3 and TRIUMPH-4 have been announced as sponsor topline results and reported by the trade and professional press; the sponsor states detailed results will be presented at future meetings and published later. None of the completed phase 3 studies had results posted on ClinicalTrials.gov when this file was written. Figures quoted from those announcements are sponsor-reported and have not been through external review. source
The evidence base is almost entirely industry-run. 32 of the 33 registered studies list Eli Lilly and Company as lead sponsor, and the published trials are authored substantially by Lilly employees and shareholders, as their own declaration-of-interests statements record. This is normal for a drug in development and it is not an accusation; it does mean there is no large independent replication of any of these results. source
Long-term safety is not established. The longest published or announced follow-up in the programme is 104 weeks. Cardiovascular and kidney outcomes remain under study in TRIUMPH-Outcomes (NCT06383390), a trial with a registered enrolment of 10000 that has not reported. In TRIUMPH-3, neither the wider nor the narrower composite cardiovascular endpoint reached statistical significance, with hazard ratios of 0.82 (95% CI 0.55 to 1.22) and 1.12 (95% CI 0.64 to 1.96) respectively and confidence intervals wide enough to be consistent with benefit or with harm. source
Discontinuation because of adverse events was common at the higher doses and rose with dose. TRIUMPH-1 reported discontinuation rates owing to adverse events of 4.1%, 6.9% and 11.3% across its three doses against 4.9% with placebo. TRIUMPH-4 reported 12.2% and 18.2% at its two doses against 4.0% with placebo. A result reported for people who stayed in a trial is not a result for everyone who started it. source
Adverse events were frequent, not incidental. In the phase 3 obesity trial TRIUMPH-1, participants on the highest dose reported nausea (42.4%), diarrhoea (32.0%), constipation (26.1%) and vomiting (25.3%), and dysesthesia and urinary tract infections were reported in around one in ten participants on the highest doses. These were events recorded under medical supervision, with the option to reduce dose or stop. source
Populations the trials excluded were not studied, and the trials cannot be read across to them. A published case report describes a man in his mid-30s with longstanding type 1 diabetes who presented with severe vomiting, diarrhoea, hyperglycaemia, ketonaemia and acute kidney injury shortly after self-administering an online-purchased product marketed as retatrutide. The report's authors state that retatrutide "has no established role in type 1 diabetes mellitus", and that causation cannot be established in the case because a concurrent Shigella flexneri infection was also present. source
There is no established storage condition, in-use period, or shelf life. No approved product label exists in any country and there is no pharmacopoeial monograph, so nobody with the standing to determine handling conditions has done so. No peer-reviewed forced-degradation or shelf-life study for retatrutide was located. source
The published research does not establish a dose, a route, a schedule, a duration, or a formulation for use by anyone outside a clinical trial. The escalation schedules used in the trials were designed alongside supervision, monitoring and stopping rules that do not exist outside them, and the trials were not designed to answer what happens without those.
The anti-doping position is unresolved rather than permissive. No anti-doping authority statement naming retatrutide was retrievable during data entry. The statement that does exist covers GLP-1 agonists as a class and names only approved products; whether it reaches an unapproved triple agonist is a question this file does not answer. An anti-doping laboratory has separately published a validated detection method for retatrutide, citing increasing use among physically active populations. source
The molecular record itself carries an unresolved discrepancy. PubChem titles its record "Retatrutide (sodium salt)" while listing a formula containing no sodium, and FDA registers retatrutide and retatrutide sodium as two substances with different UNII codes. A figure attached to "retatrutide" in a third-party source cannot be assumed to belong to either form without checking which one the source meant. source
Nothing here has been evaluated for use in anyone. There is no regulatory finding of safety or effectiveness for retatrutide for any condition, anywhere. An announced intention to file a marketing application is not a finding, and this page should not be read as anticipating one.