Retatrutide: A Breakthrough Triple Agonist for Obesity, Liver Fat Reduction & Metabolic Research

Study 1: The Triple–Hormone‑Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

A pivotal randomized, double-blind, placebo-controlled Phase 2 trial conducted by Jastreboff et al. (2023) evaluated the effects of retatrutide on body weight in individuals with obesity but without type 2 diabetes over a 48-week period [1].

Study Design & Methodology

Participants were randomly assigned to receive weekly subcutaneous injections of retatrutide in varying doses (1 mg to 12 mg) or placebo. The primary outcome was percentage change in body weight, while secondary endpoints included glucose control, lipid panels, insulin levels, and HbA1c [1].

An additional substudy under the same trial focused on individuals with NAFLD (non-alcoholic fatty liver disease) using MRI to measure liver fat reduction over 24–48 weeks [2].

Key Findings

• Participants receiving 12 mg retatrutide lost 24.2% of their body weight by week 48, compared to 2.1% in the placebo group [1].

• Over 90% of participants receiving 12 mg lost at least 10% of their body weight. Remarkably, 25% lost 30% or more [1].

• Metabolic improvements included reductions in blood pressure, HbA1c, insulin resistance, and LDL cholesterol. In participants with prediabetes, 72% returned to normoglycemia [1][6].

• The most common side effects were mild-to-moderate GI symptoms, such as nausea and diarrhea, mainly during dose escalation [1][5].

Study 2: Retatrutide’s Impact on Liver Fat in NAFLD

A subgroup analysis from the TRIUMPH trial found that retatrutide reduced liver fat by up to 82% in those receiving the 12 mg dose [2]. MRI-based assessments showed nearly all participants in the 8 mg and 12 mg groups achieved liver fat normalization (<5%) [2].

Mechanism of Action

Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors. This combination uniquely addresses appetite, insulin sensitivity, and energy expenditure [3][5].

Research Applications

Retatrutide presents exciting opportunities for research across the following domains:

• Weight management mechanisms

• Incretin biology

• Liver fat metabolism and NAFLD

• Preclinical obesity and metabolic disorder models

• Endocrine signaling and energy balance

Because of its triple agonist structure, it also serves as a potent model compound for comparing to mono and dual agonists like semaglutide and tirzepatide [4].

Suggested Research Protocols

• Weekly dosing of retatrutide in rodent or cellular models

• Liver histology or MRI analogs for fat quantification

• Endocrine signaling markers (e.g., GLP-1R, GIPR, glucagon receptor)

• Weight, adiposity, and food intake measurements

• In vivo glucose tolerance tests (GTT)

⚠️ Legal Disclaimer

All products and compounds referenced are for research purposes only. Retatrutide is not approved by the FDA or Health Canada for clinical use. Not for human consumption. ExoLabz products are provided under strict “For Research Use Only” terms.

Full References

1. Jastreboff AM et al. (2023). The triple–hormone-receptor agonist retatrutide for obesity — A Phase 2 Trial. New England Journal of Medicine.
   https://www.nejm.org/doi/10.1056/NEJMoa2301972

2. Sanyal AJ et al. (2024). Retatrutide reduces liver fat in metabolic dysfunction-associated steatotic liver disease. TRIUMPH substudy.
   https://pubmed.ncbi.nlm.nih.gov/38858523

3. Lilly Medical. Retatrutide mechanism and clinical trials overview.
   https://medical.lilly.com/us/products/answers/what-retatrutide-clinical-trials-are-being-conducted-in-people-with-obesity-or-overweight-229656

4. BioSpace. Lilly’s Retatrutide Phase 2 results show up to 24.2% weight loss in obesity.
   https://www.biospace.com/article/releases/lilly-s-phase-2-retatrutide-results-published-in-nejm-show-up-to-24-2-percent-mean-weight-reduction

5. NIH PubMed. Retatrutide: pharmacology and safety review.
   https://pubmed.ncbi.nlm.nih.gov/39724554

6. American Diabetes Association. Retatrutide shows metabolic benefits beyond weight loss.
   https://diabetes.org/newsroom/american-diabetes-association-highlights-novel-agent-retatrutide-results-substantial-weight-reduction-people-with-obesity-type-2-diabetes-during-late-breaking-symposium

7. Wikipedia – Retatrutide overview
   https://en.wikipedia.org/wiki/Retatrutide