Research summary
Research HubRetatrutide
Clinical — 10 studies
Retatrutide is a peptide agonist at three hormone receptors (GIP, GLP-1 and glucagon), tested in clinical trials in obesity and type 2 diabetes. The cited trials run from phase 1 to phase 3 and sit alongside pooled analyses and one mouse study.
Updated
Being studied for
- Obesity trials in adults
- Glycaemic control in type 2 diabetes
- Body composition substudies
- GIP, GLP-1 and glucagon receptor pharmacology
- MC4R-deficient mouse models
What the research shows
Nine of the ten citations are clinical trials or reviews of them, published from 2022 to 2026. The trials are a 2022 phase 1b study in type 2 diabetes under the development code LY3437943, two 2023 phase 2 trials (one in obesity, one in type 2 diabetes), a 2025 body-composition substudy of a phase 2 diabetes trial, and TRANSCEND-T2D-1, a 2026 phase 3 trial in type 2 diabetes. Two 2025 systematic reviews cover the obesity trials, and two network meta-analyses, from 2024 and 2025, set retatrutide beside other GLP-1-based agents. The tenth is a 2026 study in MC4R knockout mice.
The phase 2 obesity trial, in adults with obesity or with overweight and a weight-related condition, reported substantial reductions in body weight at 48 weeks. In type 2 diabetes, the phase 1b study reported an acceptable safety profile with reductions in glucose and body weight, and the phase 2 trial reported clinically meaningful effects on glycaemic control, marked reductions in body weight and safety findings in line with those of GLP-1 receptor agonists. TRANSCEND-T2D-1 reported significant effects on glycaemic control and reductions in body weight with retatrutide used alone in adults not controlled by diet and exercise, with adverse events consistent with GLP-1 activity. The substudy reported a larger fall in total fat mass than placebo, with lean mass making up a share of the weight reduction similar to other agents used in obesity.
The two systematic reviews reported significant differences from placebo across the outcomes they examined. The 2025 network meta-analysis, which weighed efficacy against adverse events across GLP-1-based agents, reported a higher adverse-event risk with retatrutide. In MC4R knockout mice, a 2026 study reported significant effects on obesity for semaglutide, tirzepatide and retatrutide alike.
The obesity trial data cited here stop at phase 2, in a trial designed to find doses rather than to confirm effects, and the only cited phase 3 trial is in type 2 diabetes. One 2025 review called for further trials to give more robust results. Network meta-analyses compare agents largely through indirect evidence across separate trials, and the mouse study describes a single genetic model.
Published Research
Evidence profile
Human Phase 3 evidence
10 cited publications · 4 primary trials · 1 derived analysis
Findings below belong to the studies that reported them. They describe the material and conditions those authors used, not this product, and not an outcome to expect.
Core evidence
The publications most central to understanding this compound.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
Jastreboff AM et al. · The New England journal of medicine · 2023
Population: Adults with a BMI of 30 or higher, or 27 to under 30 with a weight-related condition
The Phase 2 obesity trial of retatrutide, a triple GIP/GLP-1/glucagon receptor agonist. The primary endpoint was percentage change in body weight at 24 weeks, with 48-week change among the secondary endpoints.
As reported by the study
- Route reported
- Subcutaneous
- Schedule
- Once weekly under the trial protocol
- Duration
- 48 weeks
“At 48 weeks, the least-squares mean percentage change in the retatrutide groups was -8.7% in the 1-mg group, -17.1% in the combined 4-mg group, -22.8% in the combined 8-mg group, and -24.2% in the 12-mg group, as compared with -2.1% in the placebo group.”
Context: Phase 2. These findings are dose-finding rather than confirmatory, and had not been replicated in a completed Phase 3 programme at the time of curation.
Supporting evidence
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
Bajaj HS et al. · Lancet (London, England) · 2026
The study reportedRetatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse event profile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes.
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
Rosenstock J et al. · Lancet (London, England) · 2023
The study reportedIn people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists. These phase 2 data also informed dose selection for the phase 3 programme.
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
Urva S et al. · Lancet (London, England) · 2022
The study reportedIn this early phase study, LY3437943 showed an acceptable safety profile, and its pharmacokinetics suggest suitability for once-weekly dosing. This finding, together with the pharmacodynamic findings of robust reductions in glucose and bodyweight, provides support for phase 2 development.
Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis
Tewari J et al. · Expert review of clinical pharmacology · 2025
The study reportedIn conclusion our analysis found retatrutide to be clinically and statistically better than placebo in the various studies outcomes. We eagerly await the conduction of further trials for more robust and substantial results.
Efficacy and safety of retatrutide for the treatment of obesity: a systematic review of clinical trials
Misra S et al. · Journal of basic and clinical physiology and pharmacology · 2025
The study reportedWeekly subcutaneous injections of retatrutide in obese patients resulted in significant weight loss and metabolic improvements compared to a placebo.
Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA
Sinha B et al. · Obesity (Silver Spring, Md.) · 2025
The study reportedRetatrutide offers superior weight loss efficacy but with a higher AE risk. Dual agonists provide a favorable efficacy-safety balance. Personalized treatment selection based on patient characteristics is recommended.
Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials
Xie Z et al. · Metabolism: clinical and experimental · 2024
The study reportedRetatrutide (both doses) and tirzepatide exhibited superior efficacy compared to other GLP-1 receptor agonists and polyagonists in reducing body weight and waist circumference.
Additional indexed literature (2)
- Clinical · SubstudyEffects 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
Coskun T et al. · The lancet. Diabetes & endocrinology · 2025 · PMID 40609566
- Preclinical · Mechanistic studyEfficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison
Hitaka K et al. · International journal of obesity (2005) · 2026 · PMID 41723268
Published studies summarised here concern the specific investigational or pharmaceutical materials and study conditions described by their authors. Their findings are not performance claims for Cobalt Peptides material. Citations verified against PubMed on 2026-09-29.
The studies summarised here are research reports; nothing on this page is guidance on use in people or animals.
Notice
All information on this page is provided strictly for laboratory research and educational purposes only.