Retatrutide

What it is

Retatrutide is a peptide drug developed by Eli Lilly that activates three hormone receptors at once: GLP-1, GIP and glucagon. The triple action is what makes it more powerful than semaglutide (GLP-1 only) or tirzepatide (GLP-1 + GIP).

In Phase II trials people lost about 24% of body weight at 48 weeks at the top dose — a number that until then had only been seen with bariatric surgery.

It is not yet approved as a medicine anywhere as of 2026. Everything sold on the research market is exactly that — a research compound.

History

First disclosed by Eli Lilly around 2021. Phase II obesity results published 2023 (NEJM). Phase III trials are ongoing as of 2026.

How it works

GLP-1 reduces appetite and slows stomach emptying. GIP modulates insulin and may protect against the muscle-loss side of weight loss. Glucagon activation is the unusual one — it nudges energy expenditure up rather than just energy intake down. The combination produces both calorie reduction and calorie burn.

Dosage

• Starting dose in trials: 2 mg once weekly for 4 weeks.
• Titration steps: 4 mg → 8 mg → 12 mg, increasing every 4 weeks if tolerated.
• Top dose tested: 12 mg weekly. Many users stop at 4–8 mg because side effects scale fast.
• Newcomer-friendly community starter: 1–2 mg weekly for the first month.

How it is taken

• Subcutaneous injection — abdomen, thigh, or back of the upper arm.
• Once weekly. Pick a day, stick to it.

How to reconstitute

• A 10 mg vial with 2 ml of BAC water gives 5 mg/ml. A 2.5 mg dose is 50 units on a 1 ml insulin syringe.
• For lower starter doses, reconstitute with more water (e.g. 4 ml) so the syringe units are easier to read.

How it should arrive

Sealed glass vial, white fluffy powder or thin white puck, intact crimped cap. Should be cold when delivered or shipped on a cold pack.

How it should look once reconstituted

Clear, colourless after reconstitution. A slight straw tint is sometimes seen but should not be cloudy.

What to expect, and when

• Appetite suppression: typically within days of the first injection.
• Weight loss: 1–2 lb per week is common at moderate doses; faster at higher doses but with more side effects.
• 24-week mark: 12–18% body weight loss is realistic at well-tolerated doses.
• 48-week mark in trial: ~24% at the top dose.

Side effects

• Nausea — almost universal during dose increases.
• Constipation, then diarrhoea, then back again.
• Sulphur burps (rotten-egg taste).
• Fatigue, low mood, irritability — common, often during titration.
• Loss of taste for previously enjoyed food.
• Muscle loss if protein intake is too low.

Risks

• Pancreatitis — rare but documented across the GLP-1 class. Severe abdominal pain that wraps to the back is a stop-immediately signal.
• Gallbladder issues — accelerated weight loss is a known gallstone risk regardless of cause.
• Thyroid C-cell tumours in rodent studies for GLP-1 agonists. Relevance to humans is unclear; family history of medullary thyroid carcinoma is a contraindication.
• No long-term human safety data for retatrutide specifically.

Potential gains

• Largest sustained weight loss of any pharmaceutical agent in development.
• Improvements in blood glucose, blood pressure, triglycerides, liver fat.
• In some users, reduced "food noise" — the constant background thought about eating.

Other useful information

Heavy resistance training and a high-protein diet are how you avoid losing lean mass alongside fat. Many users also cycle a low dose during a fat-loss phase and stop during a maintenance phase rather than running it year-round.