Retatrutide
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How this letter has changedLatest: October 2026 · Downgraded.
Weight loss rested on one phase 2 trial, Jastreboff et al. (N Engl J Med, 2023; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 37366315; 338 adults), with the not-replicated flag accurately set, and the first phase 3, Bajaj et al. (Lancet, 2026; PMID 42250575), reports glycemic and anthropometric endpoints The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. in a different population. The written rule says a single positive trial nobody has repeated is C, and the compound is not approved anywhere. Moved to C; it returns to B when a second peer-reviewed obesity trial reports. Decided October 2026 by editor adjudication (Arnold Sandlow, D.C.).PMID 37366315 PMID 42250575
Two phase 2 randomized trials (PMID 37366315, PMID 37385280) met their pre-specified primary endpoints The one outcome a trial names in advance as its main test. Results on other outcomes carry less weight. of body weight and HbA1c A blood test that reflects average blood sugar over the previous two to three months., with large dose-dependent effects. Phase 2 trials on anthropometric and biomarker A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. endpoints cap at B however large the effect, and no phase 3 outcome trial had reported at review. The material sold online under this name sits outside any pharmacy supply chain and none of this evidence applies to an unverified vial.PMID 37366315 PMID 37385280
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Retatrutide is a new weekly shot that is not yet approved anywhere. In studies, it caused large weight loss and lowered blood sugar. People with obesity lost up to about 24 percent of their body weight in under a year. No study has yet tested whether it prevents heart attacks, strokes or other illness.
A letter describes the human evidence, not the product, the manufacturer, or the intervention's worth.
Grade C: human trials exist, but they are small, mixed or not yet repeated. This is not a finding that it does not work. How to read a grade →
See the full evidence record →Weight and glycemic reduction, Grade C under the single-trial rule. Phase 3 efficacy trials have now reported, but no trial powered for clinical events has. It is not an approved medicine anywhere. What is sold online under this name is not a prescription product.
Preliminary randomized evidence, small trials, or mixed results.
Retatrutide subcutaneously once weekly at 1, 4, 8 or 12 mg with staged escalation, for 48 weeks in the phase 2 obesity trial and 36 weeks in the type 2 diabetes trial. Phase 2 doses only; no phase 3 regimen has been established.
Not an approved medicine; Lilly has said it will file for approval in the first quarter of 2027. There is no validated human outcome to track and no legitimate prescription route in the United States outside a trial or the manufacturer's pre-approval expanded-access program.
This is an investigational compound, not an approved medicine. Material sold online as retatrutide is outside any pharmacy supply chain: identity, purity, dose accuracy and sterility are unverified, and none of the trial evidence above applies to an unverified vial. Gastrointestinal adverse events were dose-dependent and common in both trials.
- PMID 37366315 →Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.
- PMID 37385280 →Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends., placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. and active-controlled, parallel-group, phase 2 trial conducted in the USA.
- PMID 42250575 →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
This record grades the drug's own evidence. What the drug does to nutrient and lean-mass status is a separate question, answered on the GLP-1 receptor agonist depletion A fall in a nutrient's level caused by a medication, for example through reduced absorption or increased loss. record, which is where the lean-mass caution and the absolute-risk figures live.
Depletion record →Primary evidenceThree papers, each linked to its PubMed record.
Jastreboff et al. (New England Journal of Medicine, 2023; PMID 37366315): phase 2, double-blind, placebo-controlled, 338 adults with obesity, 48 weeks. Pre-specified primary endpoint was percentage change in body weight at 24 weeks and it was met: -7.2% to -17.5% across doses versus -1.6% on placebo, reaching -24.2% at 48 weeks on 12 mg. Rosenstock et al. (Lancet, 2023; PMID 37385280): phase 2, 42 US centers, adults with type 2 diabetes, primary endpoint change in HbA1c at 24 weeks, with dulaglutide as an active comparator. Bajaj et al. (Lancet, 2026; PMID 42250575), TRANSCEND-T2D-1: phase 3 in people with type 2 diabetes inadequately controlled on diet and exercise. This is the first phase 3 to report in the peer-reviewed literature. Its endpoints are glycemic and anthropometric, not clinical events. Lilly has also announced topline results from TRIUMPH-1, TRIUMPH-2 and TRIUMPH-3 by press release; those are not peer-reviewed publications and EBL does not grade on them. Every reported endpoint across all of these is body weight or HbA1c rather than a clinical event. Weight loss in obesity rests on one phase 2 trial, and the compound is not approved anywhere: under the single-trial rule that is a C. It rises to B when a second trial in the same population reports in the peer-reviewed literature, and cannot reach A until a trial powered for clinical outcomes reports and is replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away.. Moved from B in October 2026 by editor adjudication. TRANSCEND-CKD and the wider TRIUMPH program are registered and had not reported clinical-event endpoints as of this review.
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