Retatrutide
Reta · LY3437943 · Triple G
Investigational weekly triple GIP/GLP-1/glucagon agonist with the largest weight loss seen yet.
Typical dose
4 mg
Once weekly
Range
1–12
mg
Half-life
6 days
see Dosing
Evidence
Human trials
Subcutaneous
What it is
Retatrutide is a 39-amino-acid peptide that activates three receptors from one molecule: GIP, GLP-1 and glucagon. It is still investigational, with no approval anywhere, but phase 3 has begun reporting: TRIUMPH-4 read out in December 2025 and the pivotal TRIUMPH-1 in May 2026, with further readouts due through the rest of 2026.
The phase 2 obesity trial reported 24.2% mean body weight loss at 48 weeks on 12 mg weekly, against 2.1% on placebo, with the curve still falling when the trial ended. Phase 3 went further still: 28.7% at 68 weeks in TRIUMPH-4 and 28.3% at 80 weeks in TRIUMPH-1, rising to about 30.3% at 104 weeks in the TRIUMPH-1 extension. Those are the largest figures any incretin has produced in a controlled setting.
The glucagon receptor arm is what separates it from tirzepatide. Glucagon agonism raises energy expenditure and drives hepatic fat mobilisation rather than only cutting intake, which is why retatrutide loses more weight per unit of appetite suppression, and also why it raises heart rate and can push glucose up if the incretin side is underdosed.
Everything sold to the public is grey-market. There is no licensed product, no pharmacopoeial reference standard for buyers to check against, and no post-marketing safety record at all.
How it works
The GLP-1 and GIP components work as they do in tirzepatide: central satiety signalling, slowed gastric emptying, glucose-dependent insulin secretion and improved adipose nutrient handling. The third component, glucagon receptor agonism, is the addition that changes the outcome. Glucagon signalling in the liver increases fat oxidation, mobilises hepatic triglyceride and raises resting energy expenditure, so retatrutide attacks both sides of the energy balance rather than just intake.
Glucagon on its own would raise blood glucose. The trick of the molecule is that the GLP-1 and GIP agonism outweighs that, so net glycaemic control still improves. It also explains the dose-dependent heart rate rise seen in trials and why the escalation schedule matters more here than with the dual agonists.
Dosing
12 mg is the highest dose studied and should be treated as the ceiling, not a starting point; it has now been taken to 68 weeks (TRIUMPH-4) and 80 weeks (TRIUMPH-1) in phase 3. Escalation was every 4 weeks in the phase 2 protocol; going faster is where the heart rate and GI problems appear.
Standard titration
| Step | Dose | Note |
|---|---|---|
| Weeks 1-4 | 2 mg | Trial starting dose; some people start at 1 mg if GLP-1 naive |
| Weeks 5-8 | 4 mg | Produced roughly 17% weight loss at 48 weeks in trial |
| Weeks 9-12 | 8 mg | Roughly 23% at 48 weeks; most of the available benefit is here |
| Week 13 onward | 12 mg | Trial maximum, 24.2% at 48 weeks; small gain over 8 mg for a clear rise in side effects |
Reconstitution calculator
Pre-loaded with Retatrutide’s vial size, water volume and typical dose. Change anything.
Typical: 4 mg · range 1–12
Draw to
40 u
0.4 mL · 4 mg
Concentration
10 mg/mL
100 mcg per unit
Doses per vial
2.5
Vial lasts
2 weeks 4 days
Draw to 40 units on the barrel.
Once mixed
Refrigerate at 2-8C and use within about 4 weeks; discard if cloudy or particulate.
A 10 mg vial with 1 mL bacteriostatic water gives 10 mg/mL, so a 2 mg dose is 20 units on a U-100 insulin syringe, 4 mg is 40 units and 8 mg is 80 units. At 12 mg weekly, use a 30 mg vial with 2 mL (15 mg/mL) to keep the dose inside one syringe. Add water slowly down the vial wall and swirl; shaking will denature it.
Storage
Before mixing
Refrigerated at 2-8C the sealed powder is stable for years; it tolerates ambient shipping, but keep it dark and dry.
After mixing
Refrigerate at 2-8C and use within about 4 weeks; discard if cloudy or particulate.
Reported benefits
- ▪28.3% mean body weight loss at 12 mg over 80 weeks in the pivotal TRIUMPH-1 phase 3 trial (24.2% at 48 weeks in phase 2), the largest reported for any incretin
- ▪Weight loss curve had not plateaued at 48 weeks, unlike semaglutide and tirzepatide
- ▪Glucagon component raises energy expenditure rather than only suppressing intake
- ▪Marked reduction in liver fat, with most trial participants clearing hepatic steatosis
- ▪Improves HbA1c, blood pressure and lipids
- ▪Once-weekly dosing on a six-day half-life
Side effects
- ▪Nausea, vomiting and diarrhoea, dose-dependent and worst during escalation
- ▪Dose-dependent heart rate increase, typically several bpm, peaking around 24 weeks
- ▪Cutaneous hyperesthesia, a distinctive skin sensitivity or tingling reported in the phase 2 trial
- ▪Transient rise in blood glucose if escalated too fast, from the glucagon arm outpacing the incretin arm
- ▪Substantial lean mass loss, magnified by how fast the weight comes off
- ▪Gallbladder events associated with rapid weight loss
- ▪No post-marketing safety data at all, and trial exposure only runs to about 80 weeks (104 weeks in the TRIUMPH-1 extension), so genuinely long-term risks remain unknown
- ▪Markedly delayed gastric emptying — the stomach can still hold solid food many hours after a meal, so any surgery, endoscopy or procedural sedation needs the drug held beforehand and the anaesthetist told, because of the aspiration risk from retained gastric contents.
- ▪Acute pancreatitis — uncommon but a recognised incretin-class risk; severe persistent upper abdominal pain radiating to the back means stop the drug and get assessed.
Do not use if
- ▪Personal or family history of medullary thyroid carcinoma or MEN2 syndrome
- ▪History of pancreatitis
- ▪Gastroparesis or other significant gastric motility disorder
- ▪Uncontrolled tachyarrhythmia or significant cardiac disease, given the heart rate effect
- ▪Pregnancy or trying to conceive
- ▪Concurrent use of any other GLP-1 or GIP agonist
Evidence level — Human trials
Controlled human clinical data exists.
Not approved in any market; an investigational drug in ongoing phase 3 trials, sold elsewhere only as an unlicensed research chemical.
Commonly run with
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
HGH
Recombinant human growth hormone, the reference compound every GH peptide tries to imitate.
2 IU · Once daily, split into two injections above about 4 IU
Retatrutide FAQ
Is retatrutide better than tirzepatide?+
On weight loss in trial conditions, yes: 28.3% at 80 weeks in the TRIUMPH-1 phase 3 trial (24.2% at 48 weeks in phase 2) against roughly 21% for tirzepatide at 72 weeks. But tirzepatide has approval, a regulated supply chain and years of post-marketing data, and retatrutide has none of those. That is the real trade.
Why does my heart rate go up on it?+
The glucagon receptor arm. The phase 2 trial saw a dose-dependent mean increase of several bpm that peaked around 24 weeks and then partly settled. A resting rise of more than about 10 bpm, or palpitations, is a reason to hold or drop a dose step.
Should I go to 12 mg?+
For most people, no. Trial data show 8 mg gave about 22.8% and 12 mg about 24.2% at 48 weeks, so the top step buys roughly 1.4 percentage points for a clear increase in nausea and heart rate. 8 mg is where the risk-to-benefit curve flattens.
Can I switch straight over from tirzepatide?+
Not at an equivalent dose. Retatrutide adds a receptor tirzepatide does not touch, and the glucagon component needs its own tolerance build. Restart at 2 mg even if you were sitting on 15 mg tirzepatide, and escalate on the four-week schedule.
How do I know what I actually bought?+
You do not, without testing. There is no approved retatrutide product, so there is no legitimate pharmaceutical supply to compare against and no reference standard for a home check. A batch-specific third-party HPLC and mass spec report is the only meaningful evidence, and it verifies identity and purity, not sterility.
References
- 1.Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial — New England Journal of Medicine (2023) PMID 37366315
- 2.LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept — Cell Metabolism (2022) PMID 35985340
- 3.LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial — The Lancet (2022) PMID 36354040
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