Weight Loss

Retatrutide

Also known as: LY3437943, Triple G

Clinical Trials
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Key Facts: Retatrutide

Category
Weight Loss
FDA Status
Not FDA Approved
Clinical Status
Phase 3 Clinical Trials - TRIUMPH-1 pivotal trial (May 2026): 28.3% mean weight loss at 80 weeks (12 mg), 45% of patients lost 30%+ of body weight, the largest weight loss of any Phase 3 obesity drug to date. NDA submission expected late 2026 to Q1 2027
Administration
Subcutaneous injection weekly
Typical Dose
4-12 mg weekly
Frequency
Once weekly, same day each week
Duration
Long-term use expected
Also Known As
LY3437943, Triple G

Mechanism of Action

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.

Research Summary

The key human evidence is the phase 2 trial by Jastreboff and colleagues, published in the New England Journal of Medicine in 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, hinting the ceiling could be even higher. Among participants with prediabetes at baseline, a large majority returned to normal blood sugar. Side effects were dominated by gastrointestinal issues like nausea, vomiting, and diarrhea, the familiar pattern for this drug class, and were mostly dose-dependent. These are genuinely strong phase 2 results, but they are phase 2: larger and longer phase 3 trials are underway to confirm safety and durability, and retatrutide sold outside of trials is not an approved, quality-controlled medicine.

Trial Progress:Phase III
Pre
I
II
III
IV
FDA

Dosing Information

Human Trials·Human studies conducted, not FDA approved

Typical Dosing

Community experience

Common Dose

4-12 mg weekly

Range

1-12 mg weekly (titrate up slowly)

Frequency

Once weekly, same day each week

Triple agonist (GLP-1/GIP/glucagon). Start low (1-2 mg) and titrate up to minimize GI side effects. Not yet FDA approved but available through compounding.

Research Dosing

Scientific studies

Doses from clinical trials

Timing & Administration

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.

Possible Side Effects

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)
  • Currently in Phase 3 trials

References

Research This Peptide Further

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Retatrutide from $81/kit

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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 a phase 2 trial it produced some of the largest weight loss ever recorded for a drug, up to roughly 24 percent of body weight at the top dose. It is investigational, made by Eli Lilly, and not yet FDA approved as of 2026.

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 Clinical Trials - TRIUMPH-1 pivotal trial (May 2026): 28.3% mean weight loss at 80 weeks (12 mg), 45% of patients lost 30%+ of body weight, the largest weight loss of any Phase 3 obesity drug to date. NDA submission expected late 2026 to Q1 2027

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 (titrate up slowly). 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

FDA

Semaglutide 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 Loss

Tirzepatide

FDA

Tirzepatide 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 Loss

Survodutide

Clinical Trials

Survodutide is an injectable dual agonist that hits both the GLP-1 and glucagon receptors, developed by Boehringer Ingelheim and Zealand Pharma. 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 mid-2026.

Weight Loss

Cagrilintide

Clinical Trials

Cagrilintide (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 Loss

Eloralintide

Clinical Trials

Eloralintide (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.

Weight Loss

Orforglipron

FDA

Orforglipron 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 Loss

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