Retatrutide
Also known as: LY3437943, Triple G
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Key Facts: Retatrutide
- Category
- Weight Loss
- FDA Status
- Not FDA Approved
- Clinical Status
- Phase 3 complete for obesity, not FDA approved. TRIUMPH-1 (topline May 2026): 28.3% mean weight loss at 80 weeks on 12 mg (efficacy estimand), with 45% of that group losing 30% or more. TRIUMPH-2 (type 2 diabetes plus obesity, 20.8% at 12 mg) and TRIUMPH-3 (severe obesity plus cardiovascular disease, n=1,949, 22.6% at 12 mg) both met their primary endpoints (July 23, 2026). Lilly moved its FDA submission to Q1 2027 to finish manufacturing and quality data. FDA has stated compounded retatrutide does not qualify for the 503A or 503B exemptions, has sent warning letters to 'research use only' sellers, and Lilly sued six sellers in August 2026.
- Banned in Sport (WADA)
- Not named on the WADA list, but WADA's S0 catch-all bans any substance without human therapeutic approval, which covers it until it is approved. Prohibited at all times.
- Administration
- Subcutaneous injection weekly
- Typical Dose
- 4-12 mg weekly
- Frequency
- Once weekly, same day each week
- Duration
- Long-term use expected
How does Retatrutide work?
Retatrutide combines three hormone signals into one molecule. The GLP-1 component curbs appetite and slows stomach emptying, the GIP component supports insulin response and may improve how fat tissue handles nutrients, and the added glucagon receptor activity is the novel piece: glucagon can increase energy expenditure and fat burning in the liver. The idea is that two arms cut how much you eat while the third raises how much you burn, which is why retatrutide is thought to push weight loss further than GLP-1-only drugs like semaglutide or even the dual GIP/GLP-1 agonist tirzepatide. The exact contribution of each receptor in humans is still being worked out, so consider the glucagon-driven energy-expenditure story a strong hypothesis rather than fully nailed down.
What does the research show?
The first big human evidence was the phase 2 trial by Jastreboff and colleagues (New England Journal of Medicine, 2023), which randomized 338 adults with obesity (without type 2 diabetes) over 48 weeks. Mean weight reduction reached about 24 percent at the 12 mg dose, and weight loss had not clearly plateaued by week 48. In a liver-fat substudy of 98 participants, liver fat dropped by about 81 to 82 percent at the 8 and 12 mg doses by week 24. Phase 3 has since read out: in TRIUMPH-1, Lilly reported mean weight loss of 19.0, 25.9 and 28.3 percent at 4, 9 and 12 mg over 80 weeks versus 2.2 percent on placebo (efficacy estimand, which assumes people stayed on the drug; analyses counting everyone randomized come out a few points lower). TRIUMPH-2 (type 2 diabetes plus obesity) reached about 20.8 percent at 12 mg, and TRIUMPH-3 (severe obesity plus heart disease) about 22.6 percent. Side effects were dominated by dose-dependent gastrointestinal issues like nausea, vomiting, and diarrhea, plus a dysesthesia (skin sensitivity) signal at the top dose. Retatrutide sold outside of trials is not an approved, quality-controlled medicine.
What doses have been studied?
Typical Dosingⓘ
Community experience
4-12 mg weekly
1-12 mg weekly, escalated gradually
Once weekly, same day each week
A triple agonist of the GLP-1, GIP and glucagon receptors. Reported protocols begin at 1-2 mg and escalate; in phase 2, starting at 2 mg caused fewer GI events than starting at 4 mg. Not approved, and FDA says it cannot be legally compounded, so anything sold outside trials is unregulated.
Research Dosingⓘ
Scientific studies
Doses from clinical trials
Doses from Studies
0.5mg weekly (starting)
Phase 2 T2D Trial, Lancet 2023 - 0.5mg maintenance arm with no escalation ↗
4mg weekly (maintenance)
8mg weekly (maintenance)
12mg weekly (highest studied)
Phase 2 Obesity Trial, NEJM 2023 - Maximum dose showing 24% weight loss ↗
Duration
Long-term use expected
Administration
Subcutaneous injection weekly
When and how is Retatrutide taken?
Best Time to Take
Morning, same day each week
Once weekly, same day and time
Food Recommendation
With or without food
Why This Timing?
As a triple agonist, consistent weekly timing is important. Morning allows for side effect monitoring.
What are the side effects of Retatrutide?
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Nausea (dose-related)
- ●Diarrhea
- ●Vomiting
- ●Constipation
- ●Heart rate increases
- ●Hypersensitivity reactions
- ●Dysesthesia - skin sensitivity/tingling (~21% at highest dose, TRIUMPH-4 data)
- ●Pancreatitis (rare)
References
- https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
- https://mediacenteratypon.nejmgroup-production.org/NEJMoa2301972.pdf
- https://pace-cme.org/news/results-of-phase-2-trial-with-gip-glp-1-and-glucagon-receptor-agonist-to-treat-obesity/2456473/
- https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
- https://azdo.gov/sites/default/files/2025-04/retatrutide-letter-to-fsmb.pdf
- https://www.fiercepharma.com/pharma/lilly-takes-6-companies-court-selling-retatrutide-knockoffs
Research This Peptide Further
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Frequently Asked Questions
What does Retatrutide do?
Retatrutide is the heavy hitter of the new weight-loss drugs: a once-weekly injectable peptide that hits three receptors at once - GIP, GLP-1, and glucagon - earning it the nickname triple-G agonist. In phase 2 it produced about 24 percent weight loss at the top dose, and in the phase 3 TRIUMPH-1 trial Lilly reported 28.3 percent at 12 mg over 80 weeks. It is investigational, made by Eli Lilly, and not FDA approved; Lilly plans to file with the FDA in the first quarter of 2027. Because it is not an approved drug, FDA says it cannot be legally compounded.
How does Retatrutide work?
Retatrutide combines three hormone signals into one molecule. The GLP-1 component curbs appetite and slows stomach emptying, the GIP component supports insulin response and may improve how fat tissue handles nutrients, and the added glucagon receptor activity is the novel piece: glucagon can increase energy expenditure and fat burning in the liver. The idea is that two arms cut how much you eat while the third raises how much you burn, which is why retatrutide is thought to push weight loss further than GLP-1-only drugs like semaglutide or even the dual GIP/GLP-1 agonist tirzepatide. The exact contribution of each receptor in humans is still being worked out, so consider the glucagon-driven energy-expenditure story a strong hypothesis rather than fully nailed down.
Is Retatrutide FDA approved?
No, Retatrutide is not currently FDA approved. Current status: Phase 3 complete for obesity, not FDA approved. TRIUMPH-1 (topline May 2026): 28.3% mean weight loss at 80 weeks on 12 mg (efficacy estimand), with 45% of that group losing 30% or more. TRIUMPH-2 (type 2 diabetes plus obesity, 20.8% at 12 mg) and TRIUMPH-3 (severe obesity plus cardiovascular disease, n=1,949, 22.6% at 12 mg) both met their primary endpoints (July 23, 2026). Lilly moved its FDA submission to Q1 2027 to finish manufacturing and quality data. FDA has stated compounded retatrutide does not qualify for the 503A or 503B exemptions, has sent warning letters to 'research use only' sellers, and Lilly sued six sellers in August 2026.
Is Retatrutide banned in sport?
Not named on the WADA list, but WADA's S0 catch-all bans any substance without human therapeutic approval, which covers it until it is approved. Prohibited at all times.
What are the side effects of Retatrutide?
Reported side effects include: Nausea (dose-related), Diarrhea, Vomiting, Constipation, Heart rate increases. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Retatrutide?
Community-reported common dose: 4-12 mg weekly (Once weekly, same day each week). Range: 1-12 mg weekly, escalated gradually. Administration: Subcutaneous injection weekly. Community-reported doses. Not medical advice. Consult healthcare provider.
Related Peptides
Peptides commonly compared with Retatrutide or used in similar applications.
Semaglutide
FDASemaglutide is a GLP-1 receptor agonist, a peptide engineered to mimic the natural gut hormone GLP-1 but with a roughly week-long half-life so it can be dosed once weekly. It is FDA-approved and sold as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for chronic weight management, with cardiovascular benefit also on the label. This is one of the most rigorously tested peptides in existence, backed by large randomized trials, so the evidence here is in a completely different league from research-only peptides.
Weight LossTirzepatide
FDATirzepatide is a single peptide that activates two receptors at once: GIP and GLP-1, the two main incretin hormones your gut releases after eating. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for chronic weight management and obstructive sleep apnea, and it has produced the largest weight-loss numbers of any approved drug to date. Like semaglutide, this is a heavily trialed, fully approved medicine, not a gray-market research compound.
Weight LossOrforglipron
FDAOrforglipron is Eli Lilly's oral, once-daily GLP-1 receptor agonist, and the headline is that it is a small molecule, not a peptide, so it survives the gut and can be taken as a plain pill with no food or water restrictions. It is being developed for type 2 diabetes and obesity and has completed multiple successful Phase 3 trials. As of mid-2026 it is filed for regulatory review but not yet approved.
Weight LossSurvodutide
Clinical TrialsSurvodutide is an injectable dual agonist that hits both the GLP-1 and glucagon receptors, discovered by Zealand Pharma and developed by Boehringer Ingelheim. It is being tested for obesity and for fatty liver disease (MASH), and it carries an FDA Breakthrough Therapy designation for MASH. It is still investigational and not approved for any use as of October 2026, and no US filing has been publicly announced.
Weight LossCagrilintide
Clinical TrialsCagrilintide (also called AM833) is a long-acting synthetic analog of amylin, the gut-brain satiety hormone co-secreted with insulin by pancreatic beta cells. It is an investigational once-weekly injectable being developed by Novo Nordisk for obesity, most prominently as the amylin half of CagriSema (cagrilintide plus semaglutide). It is not yet approved as a standalone drug, but it has cleared phase 2 trials and is in late-stage development.
Weight LossEloralintide
Clinical TrialsEloralintide (Eli Lilly code LY3841136) is an investigational, long-acting, selective amylin receptor agonist given as a once-weekly subcutaneous injection for obesity. Amylin is the satiety hormone your pancreas releases alongside insulin, and eloralintide is built to mimic it without the gut side effects that sink most appetite drugs. It is not approved anywhere yet, but it has cleared Phase 1 and a 263-person Phase 2 trial with weight loss up to roughly 20 percent, and Lilly has said it is moving into Phase 3.
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