Retatrutide
Also known as LY3437943, Triple G, GGG tri-agonist
Retatrutide is a once-weekly peptide that activates GLP-1, GIP and glucagon receptors together. Phase 2 data showed about 24 percent weight loss at 48 weeks, the largest figure reported for any single compound, but it is still years from approval.
Reviewed by the amino101 editorial team. , first published .
Quick start
What people commonly do. Not a prescription.- Typical dose
- 1 to 2 mg (starting dose)
- How often
- once weekly
- Where
- Subcutaneous, abdomen, thigh or upper arm, rotate sites
- Timing
- same day each week, any time, with or without food
- Effects timeline
- appetite drop within 1 to 2 weeks, resting heart rate rise in the first month, weight loss builds from about week 4 and was still going at 48 weeks in phase 2
- Storage
- fridge 2 to 8 C once mixed, use within 4 weeks
- Cycle length
- ongoing in trials, escalated every 4 weeks toward 4, 8 or 12 mg
- Break between
- none planned; no withdrawal data yet, assume regain and taper down if stopping
1 to 2 mg is the trial starting point. Maintenance arms in phase 2 were 4, 8 and 12 mg weekly; community users mostly hold at 4 to 8 mg, and 12 mg is rarely needed to get results.
Overview
Retatrutide is Eli Lilly's follow-up to tirzepatide: a single peptide that activates three receptors, GLP-1, GIP and glucagon. The glucagon component is the new piece. Glucagon receptor activation raises energy expenditure and pushes the liver to burn fat, which in theory adds a calories-out lever to the appetite lever that GLP-1 drugs already pull. It is a lipidated peptide dosed once weekly, same as its predecessors.
The Phase 2 obesity trial published in 2023 is why everyone is paying attention. At the 12 mg weekly dose, participants lost an average of about 24 percent of body weight at 48 weeks, and the curves had not flattened when the trial ended. A liver fat substudy showed most participants on the higher doses reaching normal liver fat. A separate Phase 2 in type 2 diabetes produced strong HbA1c reductions on top of the weight loss.
Phase 3 (the TRIUMPH program) is ongoing. Lilly reported topline results from one of those trials in late 2025 showing weight loss in the high 20s percent range at 68 weeks, but that came from a press release, not a peer-reviewed paper. There is no approved product anywhere, so everything sold as retatrutide is grey-market material of unverified purity, and the hype around it has attracted plenty of low-quality product.
How it works
Three receptors, three jobs. GLP-1 activation lowers appetite, slows gastric emptying and improves glucose-dependent insulin secretion. GIP activation adds to appetite suppression, may improve fat tissue metabolism and appears to reduce nausea. Glucagon receptor activation is the distinctive part: it increases resting energy expenditure, drives fat oxidation in the liver and lowers liver fat. On its own, glucagon would raise blood glucose, but the two incretin components offset that. Retatrutide is deliberately a weak GLP-1 agonist molecule for molecule and a stronger GIP and glucagon agonist, a balance chosen so that the metabolic effects come through without hyperglycemia.
Where the research stands
Chronic weight managementStrong evidence
- Obesity without diabetes. Phase 2 RCT, about 24 percent mean loss at 12 mg over 48 weeks with the curve still falling.
- Phase 3 program. TRIUMPH RCTs, sponsor-reported topline results in late 2025 exceeded phase 2 numbers; peer-reviewed data pending.
Fatty liver diseaseModerate evidence
- Liver fat reduction (MASLD). Phase 2a substudy, over 80 percent of participants on higher doses reached normal liver fat by week 48.
Type 2 diabetesModerate evidence
- Glucose control. Phase 2 RCT, HbA1c down by up to about 2 points with roughly 17 percent weight loss at the top dose.
Obesity-related joint painEmerging
- Knee osteoarthritis pain. Phase 3 TRIUMPH-4 topline from the sponsor reported pain improvement alongside weight loss; not yet published.
- human RCT12 mg weekly produced about 24 percent mean weight loss at 48 weeks in adults with obesity, with loss still ongoing at trial end (Phase 2).
- human RCTOver 80 percent of participants with fatty liver on the higher doses reached normal liver fat by week 48 (Phase 2 substudy).
- human RCTLowered HbA1c by up to about 2 percentage points in type 2 diabetes alongside roughly 17 percent weight loss at the top dose (Phase 2).
- human RCTSponsor-reported Phase 3 topline results in late 2025 exceeded the Phase 2 figures; full peer-reviewed data still pending.
- human RCTHeart rate rose by several beats per minute early in treatment and drifted back toward baseline over time.
Rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Levels over time
Modeled from the half-life. Illustrative, not measured.Dosing every 7 d with a half-life of 6 d means each dose lands on top of what is left from the last one. Levels climb to about 1.8 times a single dose before settling, roughly 24 d in.
The six-day half-life supports once-weekly injections and means each dose step accumulates for roughly a month, which is why trials waited 4 weeks between increases and why early side effects can keep building for two to three weeks after a step.
Retatrutide dosage and protocols
Not cycled. Trials used a 4-week step schedule starting at 1 or 2 mg, and the phase 2 dropouts were driven by fast escalation, so community protocols hold each step for the full 4 weeks and stop climbing once appetite is controlled. No withdrawal data exist, so stopping should be treated as a taper.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Weeks 1 to 4, tolerance | 1 to 2 mg | once weekly | Subcutaneous |
| Weeks 5 to 8 | 2 to 4 mg | once weekly | Subcutaneous |
| Weeks 9 to 12 | 4 to 8 mg | once weekly | Subcutaneous |
| Week 13 onward, if still needed | 8 to 12 mg | once weekly | Subcutaneous |
| Low-dose hold (common community pattern) | 4 mg | once weekly | Subcutaneous |
Food and time of day do not matter for the injection. Evening dosing helps sleep through the worst of the nausea. The glucagon component raises heart rate for the first month or two, so heavy stimulant use or intense training right after a dose step is worth easing off. Keep the weekday consistent.
Trials started at 1 or 2 mg weekly and increased every 4 weeks toward 4, 8 or 12 mg. Community users who copy the trial schedule usually hold at the lowest dose that controls appetite; 12 mg is not needed to get results.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 10 mg | 1 mL | 10 mg/mL | 10 units |
| 20 mg | 2 mL | 10 mg/mL | 10 units |
| 30 mg | 3 mL | 10 mg/mL | 10 units |
How to reconstitute Retatrutide
- 1
Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.
- 2
Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.
- 3
Draw the bacteriostatic water into a mixing syringe.
- 4
Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.
- 5
Swirl gently or leave it to dissolve. Do not shake.
- 6
Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.
- 7
Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.
- Full walkthrough with syringe reading and site rotation: reconstitution guide.
- ✓White, fluffy cake
Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.
- ✓Clear after mixing
Once dissolved the solution should be water-clear with nothing floating in it.
- !Slight clumping
Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.
- ✕Collapsed or melted
Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.
- ✕Cloudy or particles
Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.
- Week 1 to 4
Appetite drops, nausea and possible skin tingling appear, resting heart rate may climb a few beats. Modest loss at the starting dose.
- Week 4 to 12
Loss accelerates with each step, often 2 pounds or more a week, GI effects flare after each increase.
- Month 3 to 6
Steady loss at maintenance dose, heart rate drifts back toward baseline, side effects ease.
- Month 6 to 12
Loss continues without a clear plateau in phase 2 data; body composition and protein intake matter increasingly.
Interactions and stacking
Cagrilintidecaution
Community stack with no data; the combined satiety and slowed stomach can push people into under-eating and severe nausea.
Tirzepatideavoid
Overlapping GIP and GLP-1 activity, nothing to gain from stacking two weekly incretin drugs.
Semaglutideavoid
Same reasoning, duplicated GLP-1 agonism with additive side effects.
Insulin and sulfonylureascaution
Hypoglycemia risk in combination; reduce the other drug and watch glucose.
Stimulants and heart-rate raising drugscaution
Retatrutide raised resting heart rate more than semaglutide in trials, so stacking caffeine, pre-workouts or decongestants can compound that.
Oral medications with a narrow margincaution
Delayed gastric emptying changes absorption of drugs like warfarin and levothyroxine during titration.
MOTS-ccompatible
Community pairing to protect exercise capacity during loss; untested together.
Safety
- ▲Nausea, vomiting and diarrhea, rougher than semaglutide in the early weeks
- ▲Resting heart rate up by several beats per minute for the first months
- ▲Skin tingling or heightened skin sensitivity (dysesthesia)
- ▲Constipation and reflux
- ▲Injection site reactions
- ▲Fatigue and reduced exercise tolerance early on
- ▲Same GI side effects as the rest of the class, and the glucagon component can make early weeks rougher. Fast escalation was the main driver of dropouts in Phase 2.
- ▲Heart rate increases were larger than with semaglutide. People with arrhythmias or uncontrolled blood pressure should be careful.
- ▲A minority of Phase 2 participants reported skin tingling or heightened sensitivity (dysesthesia), which usually resolved.
- ▲No approved product exists, so every vial is unverified. Purity, concentration and even identity vary between suppliers.
- ▲Assume the class thyroid, pancreatitis and gallbladder warnings apply.
- ■Resting heart rate stays more than about 20 beats above your baseline or you get palpitations
- ■Severe or persistent abdominal pain, a possible pancreatitis sign
- ■Vomiting that prevents keeping fluids down
- ■Skin sensations that spread or worsen rather than fading
- ■A neck lump, hoarseness or trouble swallowing
Community poll
Self-reported by visitors. Not clinical evidence.Retatrutide: frequently asked
Is retatrutide better than tirzepatide?
The Phase 2 weight loss numbers were larger, about 24 percent at 48 weeks versus around 20 percent for tirzepatide at 72 weeks, and the liver fat data are striking. But there has been no head-to-head trial, the Phase 3 data are not published, and tirzepatide has years of real-world safety behind it. On paper, yes; in practice, unproven.
When will it be approved?
Phase 3 trials run through 2026 and beyond. Even if everything goes well, an FDA decision is likely in 2027 at the earliest, with launch some time after that.
Why add glucagon to a weight loss drug?
Glucagon raises energy expenditure and burns liver fat, which are effects GLP-1 alone does not produce. It would normally raise blood sugar, but the GLP-1 and GIP activity cancel that out. The result is a drug that both cuts intake and raises output.
What dose are people actually using?
Most community protocols start at 1 to 2 mg weekly and hold at 4 to 8 mg. The 12 mg trial dose is rarely necessary and comes with more side effects. Because it is grey-market, the label dose and the actual dose are not always the same thing.
References
- Triple-hormone-receptor agonist retatrutide for obesity, a phase 2 trial. New England Journal of Medicine, 2023
- Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. The Lancet, 2023
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine, 2024
- 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