Mechanism
How Retatrutide Works: The Triple Receptor Mechanism
A plain-English breakdown of GLP-1, GIP, and glucagon — and why all three together beats two.
Retatrutide is an investigational triple receptor agonist targeting GLP-1, GIP, and glucagon — showing unprecedented weight loss results in Phase 2 trials.
Retatrutide (also known by its development code LY3437943) is an investigational once-weekly injectable medication developed by Eli Lilly and Company. Unlike earlier GLP-1 drugs such as semaglutide (Ozempic/Wegovy), retatrutide is a triple agonist — simultaneously activating three hormone receptors involved in appetite regulation and energy metabolism.
The drug mimics the action of three naturally occurring hormones: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon. This triple mechanism is thought to produce more powerful and sustained weight loss than single or dual agonists.
Read Full Overview →Incretin-based triple receptor agonist (GLP-1/GIP/Glucagon)
Eli Lilly and Company — Indianapolis, Indiana
Phase 3 clinical trials ongoing (TRIUMPH program)
Stimulates insulin secretion, reduces glucagon release, slows gastric emptying, and suppresses appetite signals in the brain — the same pathway as Ozempic and Wegovy.
Enhances the insulin response after meals and may improve the tolerability of the GLP-1 component, reducing nausea. GIP also plays a role in fat storage regulation.
This is the key differentiator from tirzepatide. Glucagon activation increases energy expenditure (calorie burning) and stimulates fat breakdown in the liver, potentially accelerating weight loss beyond dual agonists.
Eli Lilly initiates Phase 1 safety and pharmacokinetics studies for LY3437943, confirming the drug's tolerability profile in healthy volunteers.
A 24-week randomized controlled trial in 338 adults with obesity reported up to 24.2% mean body weight reduction at the highest dose — results published in The New England Journal of Medicine.
Eli Lilly expands the TRIUMPH program into large-scale Phase 3 trials across multiple indications including obesity, type 2 diabetes, and non-alcoholic fatty liver disease (MASH).
If Phase 3 data supports efficacy and safety, Eli Lilly is expected to file a New Drug Application (NDA) with the FDA, potentially targeting approval in 2026 or 2027.
Triple agonist vs. the world's most prescribed GLP-1 drug. How big is the weight loss gap?
Read comparison →Both are from Eli Lilly. What does adding the glucagon receptor actually add over the dual agonist?
Read comparison →Weekly injection vs. daily pill — also both from Lilly. Which approach wins on outcomes vs. convenience?
Read comparison →The complete 2025 table — every approved and investigational weight loss drug ranked side by side.
See full table →Why the glucagon pathway makes retatrutide a uniquely promising candidate for fatty liver disease.
Read guide →A plain-English breakdown of GLP-1, GIP, and glucagon — and why all three together beats two.
A breakdown of adverse events reported in Phase 2 trials, including nausea, vomiting, and gastrointestinal effects.
When will it be available? Who is eligible? How does the dosing work? We answer the most common questions.