Retatrutide
Triple GLP-1 / GIP / glucagon receptor agonist
- Class
- Triple agonist
- Half-life
- ~6 days
- Route
- Subcutaneous (SubQ)
- Cadence
- Weekly
- Evidence
- Human clinical trials
Overview
Retatrutide is the most aggressive weight-loss peptide in development right now. A once-weekly injection that hits three different metabolic switches at once — the two that tirzepatide hits (GLP-1 and GIP, which control appetite and how you handle food) plus a third one, glucagon, that turns up your body's energy burn.
In the Phase 2 trial (NEJM 2023), people on the 12 mg dose lost about 24% of their body weight over 48 weeks — meaningfully more than tirzepatide or semaglutide head-to-head. That's the highest weight-loss number any peptide has produced in a controlled trial to this point. Phase 3 (the TRIUMPH program) is currently running for obesity, type-2 diabetes, and fatty liver disease.
It is NOT approved yet — anywhere. Nothing you buy is FDA-cleared, and the only safety data that exists is from the trials themselves (~1-2 years). The glucagon part also brings new wrinkles you don't get with tirzepatide or semaglutide: heart rate runs higher, and blood sugar can transiently rise before the GLP-1/GIP effects kick in.
In the pivotal Phase 3 TRIUMPH-1 trial (announced May 2026), people on the 12 mg dose lost 28.3% of their body weight at 80 weeks, with 45.3% achieving ≥30% weight loss. A blinded extension in participants with baseline BMI ≥35 showed 30.3% weight loss at 104 weeks — weight reduction matching bariatric surgery outcomes.
Safety considerations
A few of the safety signals worth knowing — the full list, with dosing context and what to monitor, is inside AIx Core.
- Not approved by ANY regulator. The molecule on the research market is unapproved, unregulated, and the long-term safety is genuinely unknown (the trials are only 1-2 years long).
- GI side effects are the dominant reason people quit — nausea, vomiting, sometimes severe diarrhoea, especially during the dose ramp. If you skip the slow titration, you'll feel it.
- The glucagon part raises resting heart rate noticeably and can transiently bump blood sugar and blood pressure. People with cardiovascular issues should be cautious.
+ 3 more safety notes inside AIx Core →
Commonly monitored
Markers and signals people track when researching Retatrutide.
- Resting heart rate — the glucagon component tends to nudge this up
- Body composition (DEXA scan ideally — scale weight alone hides lean-mass loss)
- HbA1c if you're diabetic or pre-diabetic
- Liver enzymes — there's a fatty-liver indication in play, monitor that pathway
- Lipid panel + blood pressure
Frequently asked questions
What is Retatrutide?
Triple GLP-1 / GIP / glucagon receptor agonist. Retatrutide is the most aggressive weight-loss peptide in development right now. A once-weekly injection that hits three different metabolic switches at once — the two that tirzepatide hits (GLP-1 and GIP, which control appetite and how you handle food) plus a third one, glucagon, that turns up your body's energy burn.
How is Retatrutide administered?
Subcutaneous (SubQ), typically weekly.
What is the half-life of Retatrutide?
~6 days — Stays in your system about a week — supports once-weekly injection.
Is Retatrutide approved for human use?
Retatrutide is investigational — not approved by the FDA, EMA, or MHRA for human use at the time of writing.
What does the evidence show for Retatrutide?
Evidence tier: Human clinical trials. Phase 2 (Jastreboff 2023, N=338): 12 mg dose hit -24.2% body weight at 48 weeks vs -2.1% on placebo. That's the headline number that turned heads.
What is commonly monitored when researching Retatrutide?
Commonly tracked markers + signals: Resting heart rate — the glucagon component tends to nudge this up, Body composition (DEXA scan ideally — scale weight alone hides lean-mass loss), HbA1c if you're diabetic or pre-diabetic, Liver enzymes — there's a fatty-liver indication in play, monitor that pathway, Lipid panel + blood pressure.
Related compounds
Open this in AIx Core for the full picture
Mechanism breakdown, receptor pathway diagram, full safety list, monitored items, source citations, and one-tap add-to-protocol. Free with any account.