Retatrutide
LY3437943
An investigational triple agonist (GIP, GLP-1 and glucagon receptors) studied for weight loss and metabolic health
Retatrutide is an investigational peptide from Eli Lilly that activates three receptors: glucagon (GCG), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). It's studied for obesity, type 2 diabetes and related conditions. As of October 2026, Lilly has reported five positive Phase 3 trials, with mean weight loss of up to 28.7% at 68 weeks in participants who stayed on treatment (TRIUMPH-4). It isn't approved anywhere; Lilly plans to submit it to the FDA in Q1 2027. It adds glucagon receptor activity to the GIP/GLP-1 approach of tirzepatide, which is an approved prescription medicine.
Read the research profile for mechanisms, citations, and safety context before comparing vendors. View the Retatrutide research profile.
Key Benefits
Mechanism of Action
Retatrutide is a single molecule that activates three receptor pathways. GLP-1 receptor activation reduces appetite and increases insulin release after meals. GIP receptor activation adds to that insulin response and is thought to improve insulin sensitivity. Glucagon receptor activation is proposed to raise energy expenditure and increase lipolysis (fat breakdown), and it's the main feature that separates retatrutide from dual agonists. How much each pathway contributes to weight loss in people hasn't been worked out.
Dosing Guidelines
Typical Dose
2-12 mg weekly in trials (Phase 3 targets: 4, 9 or 12 mg)
Frequency
1x weekly
Duration
40-80 weeks in trials
Note: Trials gave it by subcutaneous injection once a week. In Phase 3, participants started at 2 mg and stepped up every 4 weeks to a target of 4 mg (via 2 mg), 9 mg (via 2, 4 and 6 mg) or 12 mg (via 2, 4, 6 and 9 mg). The 2023 Phase 2 trial also tested 1 mg and 8 mg, and starting at 2 mg rather than 4 mg partly reduced stomach side effects. Users on peptide forums often describe starting at 0.5 mg a week or less, sometimes split into two doses; that's community practice, not a tested protocol.
Research & Studies
Our profile of retatrutide's mechanism, trial results, reported doses and side effects, for research purposes.
Read Full ResearchIn 338 adults with obesity or overweight, weekly retatrutide gave mean weight loss of 8.7% (1 mg) to 24.2% (12 mg) at 48 weeks, vs 2.1% on placebo.
Read Full ResearchAs of October 2026, Lilly has reported five positive Phase 3 trials. In TRIUMPH-1 (80 weeks), mean weight loss was 19.0%, 25.9% and 28.3% on 4, 9 and 12 mg; in TRIUMPH-4 (68 weeks), 28.7% on 12 mg vs 2.1% on placebo. Most results so far come from company releases and conference data.
Read Full ResearchHow adding glucagon receptor activity to the GIP/GLP-1 approach of tirzepatide may raise energy expenditure, and why comparisons between the two rest on separate trials.
Read Full ResearchPotential Side Effects
Reported side effects may include:
- - Nausea, diarrhea, constipation and vomiting (most common in trials, dose-dependent; nausea in 28.6-42.4% on 4-12 mg vs 14.8% on placebo in TRIUMPH-1)
- - Skin burning or tingling (dysesthesia): 4.5-20.9% across Phase 3 trials vs up to 1.3% on placebo; also user-reported
- - Increased heart rate (dose-dependent in Phase 2, peaking around week 24)
- - Injection site reactions (5.5-12.2% vs 3.8% on placebo in TRIUMPH-1)
- - Decreased appetite, which can be excessive; some TRIUMPH-4 dropouts were for perceived excessive weight loss
- - Up to 18.2% stopped for side effects at 12 mg (TRIUMPH-4) vs 4.0% on placebo
This information is for research purposes only. Always consult with a healthcare professional.
Popular Stacking Options
Retatrutide + GHK-Cu
Some users add it hoping to support skin during rapid weight loss, based on small topical studies of skin collagen. No study has tested it alongside retatrutide, and injectable GHK-Cu has no human trials.
Shop this stackRetatrutide + BPC-157
Some users add it hoping to ease the nausea and gut discomfort common with incretin mimetics, based on rodent gut studies. BPC-157 has only small uncontrolled human pilots, and no study has tested this combination.
Shop this stackRetatrutide + MOTS-c
Some users pair it on the theory that it supports mitochondrial metabolism alongside retatrutide's effect on energy expenditure. The MOTS-c data are almost entirely from mice, and no study has tested the combination.
Shop this stackFrequently Asked Questions
How is Retatrutide different from Semaglutide or Tirzepatide?
Semaglutide activates the GLP-1 receptor. Tirzepatide activates the GIP and GLP-1 receptors. Retatrutide adds glucagon receptor activation, which is proposed to raise energy expenditure. Its Phase 3 weight loss (up to 28.7% at 68 weeks) is larger than reported in the main semaglutide and tirzepatide trials, but those comparisons come from separate trials with different populations, not head-to-head results. Semaglutide and tirzepatide are approved prescription medicines; as of October 2026, retatrutide isn't approved anywhere.
Are the side effects of Retatrutide severe?
In Phase 3 trials the most common side effects were stomach-related (nausea, diarrhea, constipation and vomiting), mostly mild to moderate and most frequent while the dose was being raised. Trials stepped the dose up every 4 weeks from 2 mg, and the Phase 2 trial found a 2 mg start caused fewer stomach effects than a 4 mg start. Skin burning or tingling (dysesthesia) is a newer signal: TRIUMPH-4 reported it in 20.9% of participants on 12 mg vs 0.7% on placebo, and Lilly describes most cases as mild. In the same trial, 18.2% of participants on 12 mg stopped treatment because of side effects. Persistent or severe symptoms are a reason to see a healthcare professional.
How quickly does Retatrutide work?
Users commonly report appetite changes within the first week or two. In trials, weight loss built gradually: the Phase 2 trial reported 17.5% at 24 weeks and 24.2% at 48 weeks on 12 mg, and TRIUMPH-1 reported 28.3% at 80 weeks on 12 mg.
Is Retatrutide safe to use long-term?
As of October 2026, it's still investigational. Phase 3 trials have run up to 80 weeks, and a TRIUMPH-1 extension followed some participants to 104 weeks. Lilly reports side effects broadly similar to other incretin-based drugs, plus dysesthesia. TRIUMPH-3 had too few heart events to show whether retatrutide changes cardiovascular risk, and Lilly is still studying cardiovascular and kidney outcomes. Safety beyond about two years isn't known. Gray-market vials add another unknown: they aren't Lilly's product, and Lilly states retatrutide can't be legally sold or marketed for human use.
Does Retatrutide cause muscle loss?
Any large calorie deficit can cost lean mass as well as fat, and as of October 2026 we didn't find published body-composition results from the Phase 3 trials. Users commonly describe eating more protein (often 1.6-2.2 g per kg of body weight, a range common in sports-nutrition guidance) and resistance training during a retatrutide research protocol to limit muscle loss. No retatrutide trial has tested those strategies.
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Semaglutide
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