Retatrutide
aka LY3437943
Triggers 3 different metabolism signals at once — appetite, insulin, and fat-burning.
Technically · Triple agonist (GLP-1 + GIP + Glucagon receptors)
In one sentence
The most aggressive weight-loss peptide in trials so far — Phase 2 hit 24% body weight loss in a year.
— Like Ozempic, but it also tells your liver to burn fat — three drugs in one shot.
Half-life
~6 days
Stays active about a week — one shot per week.
Dosing
Once weekly (half-life ~6 days)
How often you take a dose
Route
SubQ
How it goes into the body
Status
Investigational
Still in clinical trials, not on the market
What it is
A new investigational shot from Eli Lilly that hits three weight-related hormones in one go: it kills your hunger (GLP-1), helps your body handle blood sugar (GIP), and tells your liver to start burning stored fat (glucagon). In its big trial, people lost almost a quarter of their body weight in a year.
The full technical answer
A novel triple receptor agonist activating GLP-1, GIP, and glucagon receptors simultaneously. The added glucagon receptor activity drives hepatic fat oxidation in addition to the appetite-suppression seen with GLP-1 mono-agonists.
How it works
Picture three signals your body uses to manage weight. GLP-1 makes you feel full faster and longer. GIP improves how your body uses insulin after a meal. Glucagon turns up the dial on burning fat for fuel. Retatrutide flips all three at once — that's why the weight loss is so big.
The full technical answer
GLP-1 receptor activation suppresses appetite and slows gastric emptying. GIP receptor activation enhances insulin secretion. Glucagon receptor activation increases energy expenditure and lipolysis in the liver.
What the research says
Phase 2 trial (NEJM 2023) showed up to 24.2% body weight loss at 48 weeks at 12mg weekly — the largest weight reduction reported for any GLP-class compound. Phase 3 trials ongoing.
Sources: NEJM 2023 Phase 2 · ClinicalTrials.gov NCT05882045
Common dosing ranges
- Range
- Phase 2 trials tested 1, 4, 8, 12 mg weekly. Microdose protocols start at 0.25–0.5 mg.
- Frequency
- Once weekly (half-life ~6 days)
- Duration
- Trial protocols ran 48 weeks
Sources: NEJM 2023
How to take it
Practical guidance synthesized from clinical protocols, FDA labels, and clinician interviews. Always cross-check with a prescribing physician.
Best time of day
Same day each week, any time. Many users pick Friday or Saturday evening so the nausea peak happens during sleep.
With food or fasted
Doesn't matter — subcutaneous injection bypasses the gut. Some users eat lighter the day of injection to ease nausea.
How long to cycle
Long-term continuous use in trials (48 weeks). Titrate dose up slowly — most start at 0.25–0.5 mg and step up every 4 weeks.
When to get off
Drop dose down or pause if nausea persists more than 2 weeks at the new step. Stop and call a doctor for severe belly pain (pancreatitis) or any neck lumps.
Administration
Side effects
Common
- Nausea
- Diarrhea
- Vomiting
- Constipation
- Decreased appetite
Serious / theoretical
- Possible thyroid C-cell tumors (per GLP-1 class warning)
- Pancreatitis (rare)
Sources: NEJM 2023 safety data
Notes
Not FDA-approved. Eli Lilly is the developer. Often acquired from compounding pharmacies or research-grade suppliers in the US.
Further reading & listening
Where the experts go deeper.
Curated from the PeptideFacts expert directory — vetted YouTube channels, podcasts, books, and communities. No anecdote-only or supplier-affiliated picks.
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