Retatrutide

ID: retatrutide

Aliases: LY3437943, Reta, RETATRUTIDE

Type: compound

Route/form: subcutaneous injection in trials

Status: investigational

Evidence level: human RCT

Best data tier: human controlled/review

Support scope: human, non-human/mechanistic, review/regulatory

Source types: human_rct, human_trial, mechanistic, meta_analysis, preclinical, review

Linked sources: 10

Broad outcomes: Fat loss / metabolic health

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• GLP-1 receptor agonist
• GIP receptor agonist
• glucagon receptor agonist

Optimization domains

• metabolic
• obesity
• diabetes
• MASLD

Research basis

• Human phase 1b T2D and phase 2 obesity data support the GLP-1/GIP/glucagon triple-agonist concept, with large weight-loss and glycemic signals.
• The discovery/translational paper provides mechanism support: balanced GLP-1/glucagon activity, stronger GIP activity, mouse weight loss, glycemic control, and a glucagon-linked energy-expenditure component.
• MASLD/body-composition data and TRIUMPH phase 3 design make retatrutide relevant to obesity complications, liver fat, OSA, knee OA, and fat-vs-lean-mass questions.

Limits, risks, and missing evidence

• It remains investigational at this curation point, so long-term outcome and label-level safety context are incomplete.
• GI effects, heart-rate effects, gallbladder/pancreatitis class concerns, and glucagon-related physiology need trial-context interpretation.
• Large weight loss can still carry lean-mass and training-performance tradeoffs unless directly tested with body-composition and function endpoints.

Risk flags

• investigational
• metabolic endocrine
• medical supervision

Linked papers, labels, and reviews

1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
   human_rct / pubmed_retatrutide_obesity_2023
   Phase 2 obesity trial; PubMed record for NEJM paper.
2. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes
   human_rct / pubmed_retatrutide_t2d_2023
   Phase 2 type 2 diabetes trial for the GLP-1/GIP/glucagon triple agonist retatrutide.
3. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial
   human_rct / pubmed_retatrutide_masld_phase2a_2024
   Human MASLD substudy; retatrutide reduced liver fat, body weight, abdominal subcutaneous adipose tissue, and visceral adipose tissue over 24 weeks.
4. Effects of retatrutide on body composition in people with type 2 diabetes
   human_rct / pubmed_retatrutide_body_comp_t2d_2025
   Phase 2 substudy focused on body composition in type 2 diabetes; relevant to lean/fat mass interpretation of triple-agonist weight loss.
5. Retatrutide shows multiple metabolic benefits in diet-induced obese MASH mouse and hamster models
   preclinical / pubmed_retatrutide_mash_models_2026
   Adjacent animal mechanism source for liver/metabolic effects; not a substitute for human MASLD outcome data.
6. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition
   meta_analysis / pubmed_glp1_body_composition_network_meta_2025
   Network meta-analysis comparing body-composition effects across GLP-1 receptor agonists and co-agonists.
7. 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
   human_rct / pubmed_retatrutide_phase1b_t2d_2022
   Phase 1b multiple-ascending-dose retatrutide/LY3437943 trial in T2D; adds early human PK/PD, glycemic, weight, and safety context before phase 2 obesity data.
8. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept
   mechanistic / pubmed_retatrutide_discovery_clinical_poc_2022
   Discovery and translational pharmacology paper: receptor activity, obese mouse effects, energy-expenditure contribution from glucagon receptor activity, and clinical proof-of-concept bridge.
9. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials
   human_trial / pubmed_retatrutide_triumph_design_2026
   Design/rationale paper for phase 3 TRIUMPH obesity, OSA, and knee OA program; useful for current development direction and adiposity-related comorbidity framing.
10. Retatrutide-A Game Changer in Obesity Pharmacotherapy
    review / pubmed_retatrutide_review_2025
    Review synthesizing retatrutide mechanisms, clinical efficacy, metabolic outcomes, and safety; secondary support only.