THE COMPOUNDS COMPARED
Retatrutide Explained — The Triple Agonist, Its Trial Data, and How It Is Dosed
By G1 Peptides · Medically reviewed by the G1 Peptides clinical team · Updated September 24, 2026 · 3 min read
THE SHORT ANSWER
Retatrutide is a once-weekly injectable that activates GLP-1, GIP, and glucagon receptors together. In its phase 2 trial the top dose produced an average 24% body-weight reduction at 48 weeks without plateauing — the largest reported for any incretin drug. It is dosed in milligrams, escalated slowly over months, and carries the same digestive side-effect profile as the class.
What it is
Retatrutide (LY3437943) is a single peptide engineered to activate three receptors — GLP-1, GIP, and glucagon — with a fatty-acid side chain that gives it a roughly six-day half-life, so it is injected once a week. It was developed by Eli Lilly and is in phase 3 trials for obesity, type 2 diabetes, and related conditions.
Why glucagon
Glucagon's day job is raising blood sugar between meals, which sounds like the wrong thing to add to a weight-loss drug. In combination it does two useful things: it raises energy expenditure — you burn more at rest — and it drives the liver to burn fat, which is why retatrutide produced striking reductions in liver fat in trials. The GLP-1 and GIP components suppress appetite and keep glucose under control, cancelling glucagon's blood-sugar effect. The net result is more weight loss than either GLP-1 alone or GLP-1 plus GIP.
The phase 2 data
The obesity trial randomized 338 adults to placebo or retatrutide at 1, 4, 8, or 12 mg weekly for 48 weeks (Jastreboff 2023):
| Dose | Mean weight change at 48 weeks |
|---|---|
| Placebo | −2.1% |
| 1 mg | −8.7% |
| 4 mg | −17.1% |
| 8 mg | −22.8% |
| 12 mg | −24.2% |
Every participant on 8 or 12 mg lost at least 5%; most lost more than 15%. Crucially, the weight curves had not flattened at 48 weeks. Side effects were the class's digestive effects — nausea, diarrhea, vomiting, constipation — dose-dependent, mostly mild to moderate, and less frequent in the groups that escalated more slowly. Heart rate rose modestly (a few beats per minute) and trended back down by the end of the study.
How it is dosed
Trials began at 1–2 mg weekly and stepped up every few weeks. In practice, providers individualize the pace: the goal is to reach an effective dose while keeping nausea manageable, and a slower climb costs little. A typical structure:
- Start: 1 mg weekly for a few weeks.
- Escalate: 2 mg, then 4 mg, holding each step at least three to four weeks.
- Maintain: wherever effect and tolerance balance — 4, 8, or up to 12 mg.
Compounded retatrutide comes as a lyophilized vial (G1 supplies 10 mg). Reconstituted in 2 mL, a 1 mg dose is 20 units on an insulin syringe and the vial holds ten starting doses; at 8 mg the same vial is barely one dose. The retatrutide calculator converts any step to units.
What to expect
- Appetite drops within the first one to two weeks.
- Nausea, if it comes, peaks in the days after a dose increase and fades over the step.
- Weight loss is fastest in months two to six and continues more slowly after.
- Liver enzymes and liver fat tend to improve; blood pressure and triglycerides typically fall.
- Muscle loss accompanies fat loss unless you eat enough protein and train — see preserving muscle.
Who it is not for
The class contraindications apply: personal or family history of medullary thyroid carcinoma or MEN2, pregnancy, history of pancreatitis, and severe gastrointestinal disease. The full list is in who should not use peptides. Because retatrutide raises heart rate slightly, providers are cautious with significant cardiovascular disease until phase 3 data is in.
Retatrutide is prescribed at G1 after a free consultation.
FREQUENTLY ASKED
Is retatrutide FDA-approved?
Not yet — it is in phase 3 trials. It is available as a compounded prescription through licensed pharmacies where permitted, which is how G1 prescribes it after a telehealth consultation.
How much weight do people lose on retatrutide?
In the phase 2 trial, average loss at 48 weeks ranged from about 9% at 1 mg to 24% at 12 mg, and the curves were still descending at the end of the study. Individual results vary widely with dose, diet, and adherence.
How is it different from tirzepatide?
Tirzepatide targets GLP-1 and GIP; retatrutide adds glucagon receptor agonism, which increases energy expenditure and reduces liver fat. Trial weight loss was larger for retatrutide, at the cost of a slightly higher heart rate and, so far, less long-term data.
This article is educational and is not medical advice. Peptides are prescription medications; whether any of them is appropriate for you is a decision for a licensed provider who knows your history.