Content reviewed by clinical research staff

Last reviewed: March 2026Sources: PubMed, FDA, WADA Prohibited List

Evidence graded using the PeptideScholar A-D system.

Retatrutide

Triple GIP/GLP-1/Glucagon receptor agonist39 amino acids

BHuman Studies
90
Excellent Credibility
5 cited studies | Evidence level B

Retatrutide is an investigational triple-hormone receptor agonist developed by Eli Lilly. It simultaneously targets GIP, GLP-1, and glucagon receptors, achieving the highest weight loss ever reported in an obesity clinical trial — up to 24.2% at 48 weeks.

Mechanism of Action

Activates three metabolic receptors simultaneously: GIP receptors (enhances insulin secretion and fat metabolism), GLP-1 receptors (reduces appetite and slows gastric emptying), and glucagon receptors (increases resting energy expenditure and hepatic lipid oxidation, promoting ketogenesis independent of caloric intake). The triple agonism produces additive metabolic benefits beyond dual agonists.

Benefits

  • Unprecedented 24.2% weight loss in Phase 2 trials[1]
  • Superior to both semaglutide and tirzepatide in early data[1]
  • Significant liver fat reduction and MASLD improvement in dedicated Phase 2a trial[5]
  • Improved glycemic control in type 2 diabetes[2]
  • Weight loss is predominantly fat mass with relatively preserved lean mass per DEXA substudy[4]
Not medical advice - research-reported information only

This content is for informational purposes only and does not constitute medical advice.

Retatrutide - Dosing in Published Research

Reported routes: Subcutaneous injection
Phase 2 trial tested doses of 1, 4, 8, and 12 mg SC weekly with gradual dose escalation over 12–16 weeks to minimize GI side effects. Phase 3 trials (TRIUMPH program) ongoing with expected completion in 2026.

The dosing information above is sourced from published research literature and clinical trials. These are not recommendations. Individual responses vary. Always consult a healthcare provider before considering any peptide-based therapy.

Side Effects

  • Nausea, vomiting, diarrhea (dose-dependent)[1]
  • Decreased appetite[1]
  • Constipation[1]
  • Injection site reactions[1]
  • Fatigue, headache, and mild heart rate increase (less common)[1]
  • Long-term safety profile still being established[1]

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Research & Evidence

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References

  1. 1.Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.. N Engl J Med, 2023. "Retatrutide produced dose-dependent weight loss of up to 24.2% at 48 weeks — the highest ever reported in an obesity trial" [PMID: 37366315]
  2. 2.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. "Retatrutide reduced HbA1c by up to 2.16% and body weight by up to 16.94% in adults with type 2 diabetes" [PMID: 37385280]
  3. 3.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 Metabolism, 2022. "Engineered triple agonist with balanced receptor activity and weekly dosing due to lipidation for albumin binding" [PMID: 35985340]
  4. 4.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. "Retatrutide reduced total body fat mass substantially while preserving lean mass relative to diet-induced weight loss" [PMID: 40609566]
  5. 5.Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.. Nat Med, 2024. "Retatrutide significantly reduced liver fat content and improved MASLD biomarkers in a dedicated Phase 2a trial" [PMID: 38858523]

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