Retatrutide
Retatrutide (LY3437943) — GIP/GLP-1/Glucagon Triple Agonist
A novel triple receptor agonist targeting GIP, GLP-1, and glucagon receptors simultaneously, demonstrating unprecedented weight loss of up to 24% body weight in Phase II trials — the highest reported for any pharmacological agent to date.
Mechanism of Action
Retatrutide activates three complementary pathways: GLP-1R (appetite suppression, insulin secretion), GIPR (enhanced insulin response, fat metabolism), and glucagon receptor (increased energy expenditure, hepatic fat reduction). The glucagon component adds thermogenic and lipolytic effects not present in dual GIP/GLP-1 agonists.
Health Claims & Evidence
Produces up to 24% body weight reduction
Reduces hepatic steatosis and liver fat
Improves glycemic control in type 2 diabetes
Short-Term Effects
Significant appetite reduction and early weight loss within 4–8 weeks.
Long-Term Effects
Progressive weight loss up to 24% over 48 weeks in Phase II trials.
Side Effects
Nausea, vomiting, diarrhea, constipation, decreased appetite. Similar GI profile to other GLP-1 agonists.
Contraindications
Personal or family history of medullary thyroid carcinoma, MEN2. Not yet approved for clinical use.
This profile is provided for educational research only. It is not a treatment recommendation or dosing guide. Human evidence, safety information and regulatory status vary by substance. Verify primary sources and consult a qualified healthcare professional for medical decisions.
Research Papers
Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes
Jastreboff et al. · New England Journal of Medicine · 2023
Educational research only. This profile is not a treatment recommendation or dosing guide. Human evidence, safety information and regulatory status vary by substance. Consult a qualified healthcare professional for medical decisions.
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