Retatrutide is the next generation GLP-1 -- a triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Here is what Phase 2 trial data shows.
Quick Summary Retatrutide is a triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Phase 2 trial data published in the New England Journal of Medicine shows weight loss of up to 24% of body weight -- exceeding published results for semaglutide and tirzepatide. Educational purposes only -- not medical advice.
Semaglutide targets only GLP-1 receptors -- approximately 15% weight loss in STEP trials.
Tirzepatide targets GLP-1 and GIP receptors -- approximately 20-22% weight loss in SURMOUNT trials.
Retatrutide adds glucagon receptor agonism, which increases energy expenditure. This is the proposed mechanism behind superior weight loss in Phase 2 data.
Use the [free GLP-1 titration calculator](https://myprotocolstack.com/calculators) for reference and track your protocol at [myprotocolstack.com/labs](https://myprotocolstack.com/labs).
The NCT04881357 trial enrolled adults with obesity (BMI 30+) without diabetes:
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The [GLP-1 titration calculator](https://myprotocolstack.com/calculators) can generate a dated schedule for educational reference.
Fasting Glucose -- Glucagon promotes hepatic glucose production. Research protocols monitored fasting glucose closely throughout the trial.
HbA1c -- Documents the net metabolic effect of all three receptor mechanisms.
Liver Function (ALT, AST, GGT) -- Glucagon affects liver metabolism.
Lipid Panel with ApoB -- Phase 2 data showed favorable lipid changes.
Lean Mass Markers -- Creatinine, albumin, BUN.
Uric Acid -- Research shows rapid weight loss can transiently raise uric acid.
Is retatrutide FDA approved?
As of April 2026, retatrutide remains in Phase 3 trials. It is not FDA approved.
How does retatrutide compare to tirzepatide?
Phase 2 data shows greater weight loss with retatrutide than published tirzepatide Phase 3 data. Head-to-head comparisons are not yet available.
What are the main side effects studied in research?
Phase 2 data showed predominantly GI adverse effects -- nausea, vomiting, diarrhea -- predominantly during titration.
How is retatrutide administered?
Phase 2 protocol used weekly subcutaneous injection.
When might retatrutide receive FDA approval?
Phase 3 trials are ongoing. Timeline cannot be predicted with certainty.
*This article is for educational purposes only. Consult a licensed healthcare provider for guidance on any GLP-1 or investigational compound.*
*Written by the MyProtocolStack team. Last updated: April 2026.*
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