What Is Retatrutide (GLP-3)?

Retatrutide (development code: LY3437943) is an investigational weight loss and diabetes drug developed by Eli Lilly and Company. It is a once-weekly injectable peptide that simultaneously activates three hormone receptors: GLP-1, GIP, and glucagon. This triple-agonist mechanism makes it the first drug of its kind and distinguishes it from existing treatments like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound).

In clinical trials, retatrutide has produced the largest weight loss ever recorded for an anti-obesity medication — up to 28.7% body weight reduction at 68 weeks. As of early 2026, retatrutide is in Phase 3 clinical trials and has not yet been approved by the FDA. It does not have a brand name yet.

The informal nickname "GLP-3" has gained traction in consumer circles, though it is not a scientifically accurate term. More on that below.

How Retatrutide Works

Most weight loss drugs in the current generation work by mimicking gut hormones called incretins — hormones your body naturally releases after eating to regulate blood sugar and appetite. Retatrutide takes this approach further than any approved drug.

Structurally, retatrutide is a 39-amino acid peptide linked to a C20 fatty diacid moiety. The fatty acid chain extends the drug's half-life, allowing it to remain active in the body long enough for once-weekly dosing — the same pharmacological strategy used in semaglutide and tirzepatide.

What makes retatrutide different is its targets. Where semaglutide activates one receptor and tirzepatide activates two, retatrutide activates three. Each receptor triggers distinct biological effects, and the combination produces both reduced calorie intake and increased calorie expenditure — a dual mechanism that no approved obesity drug achieves.

The Three Receptors, Explained

1. GLP-1 (Glucagon-Like Peptide-1)

GLP-1 is the receptor that made Ozempic and Wegovy household names. When activated, it:

• Reduces appetite by acting on hunger-regulating centers in the brain
• Increases insulin secretion in response to food, improving blood sugar control
• Slows gastric emptying, meaning food stays in the stomach longer, prolonging the feeling of fullness

This is the best-understood mechanism in the incretin drug class and the foundation that all three generations share.

2. GIP (Glucose-Dependent Insulinotropic Polypeptide)

GIP is the second receptor, also targeted by tirzepatide (Mounjaro/Zepbound). Its effects include:

• Stimulating insulin release from the pancreas, complementing GLP-1's effect on blood sugar
• Reducing appetite through additional slowing of gastric emptying
• Potential effects on fat metabolism, though the precise role of GIP in weight loss is still an active area of research

Adding GIP to GLP-1 is what allowed tirzepatide to outperform semaglutide in head-to-head trials. Retatrutide includes this receptor as well.

3. Glucagon Receptor

This is the differentiator. Glucagon is a hormone most people associate with raising blood sugar — it signals the liver to release stored glucose. That might sound counterproductive in a diabetes or weight loss drug, but the glucagon receptor does more than regulate blood sugar:

• Increases energy expenditure, particularly by promoting thermogenesis (heat production) in brown adipose tissue — in other words, you burn more calories at rest
• Induces lipolysis — the breakdown of stored fat for energy
• Decreases lipogenesis — reduces the creation of new fat
• Reduces gastrointestinal motility, contributing to satiety

The glucagon component is what sets retatrutide apart conceptually. Semaglutide and tirzepatide work primarily by making you eat less. Retatrutide does that too, but also increases the rate at which your body burns energy. It attacks obesity from both sides of the energy balance equation.

How Retatrutide Compares to Existing Drugs

Each generation has roughly added 5-10 percentage points of weight loss over the previous one. The addition of the glucagon receptor appears to be a meaningful step forward, though direct head-to-head trials between retatrutide and tirzepatide have not been published.

For a detailed comparison, see Retatrutide vs Mounjaro vs Ozempic.

Key Clinical Results So Far

Phase 2 Trial — Obesity (48 Weeks)

Published in the New England Journal of Medicine in June 2023 (Jastreboff et al., NCT04881760), this was the trial that put retatrutide on the map. Results by dose:

The 24.2% weight loss at the highest dose exceeded what any obesity drug had achieved in a clinical trial at the time.

Phase 2 Trial — Type 2 Diabetes (36 Weeks)

Published in The Lancet in 2023 (Rosenstock et al., NCT04867785), this trial showed:

• HbA1c reduction of up to -2.02 percentage points
• Weight loss of up to -16.94% in people with type 2 diabetes
• Strong glucose control across all dose levels

Phase 3 TRIUMPH-4 (68 Weeks)

Announced by Eli Lilly in December 2025, the TRIUMPH-4 trial extended the treatment period and confirmed the Phase 2 findings:

TRIUMPH-4 also demonstrated significant pain relief in participants with knee osteoarthritis, suggesting potential benefits beyond weight and metabolism.

The Phase 3 TRIUMPH program includes five or more trials with approximately 5,800 participants enrolled in total. Additional readouts are expected throughout 2026.

For the full trial-by-trial breakdown, see Clinical Trials & Results.

Current Status

As of February 2026, retatrutide is not approved by the FDA and is not available by prescription. Here is where things stand:

• Phase 1 completed: Safety and pharmacokinetics established. Published in The Lancet in 2022 (Coskun et al., NCT04143802).
• Phase 2 completed: Strong efficacy demonstrated in both obesity and type 2 diabetes.
• Phase 3 (TRIUMPH program) underway: Multiple trials launched in 2023, with TRIUMPH-4 results announced in December 2025 and additional readouts expected throughout 2026.
• NDA filing (the formal application for FDA approval) is expected in late 2026 or early 2027, based on the Phase 3 timeline.
• FDA approval, if granted, is most likely in 2027.

Retatrutide does not yet have a brand name. Eli Lilly will announce one closer to the approval date.

For a detailed timeline with milestones, see FDA Approval Timeline.

For information on side effects observed in trials, see Side Effects & Safety.

For information on anticipated pricing and access, see Cost & How to Get It.

Where the Name "GLP-3" Comes From

If you arrived at this page searching for "GLP-3," you are not alone — but the term requires some clarification.

"GLP-3" is not a real biological designation. There is no GLP-3 receptor in the human body. The name is an informal shorthand that emerged from the pattern of incretin drug development:

• "GLP-1" drugs (semaglutide) activate one receptor — they are single agonists
• "GLP-2" is sometimes used informally for dual agonists (tirzepatide), which activate two receptors — though this is not standard terminology either
• "GLP-3" follows the same logic for retatrutide, a triple agonist activating three receptors

The term was popularized in part by Andrew Huberman on his podcast, where he discussed the next generation of weight loss drugs. It has since spread through social media, health forums, and consumer health content.

You may also see the abbreviations "GLP-3 RT" or "GLP-3 reta" — these are further shortened slang forms combining the "GLP-3" nickname with retatrutide's name. They are used interchangeably in online communities to refer to the same drug.

You will not find "GLP-3" used in any peer-reviewed medical journal, FDA filing, or official Eli Lilly communication. The correct terms are "retatrutide," "LY3437943," or "triple agonist." We use "GLP-3" on this site because it is what many people search for, but we want to be transparent that it is a colloquial term, not a scientific one.

Frequently Asked Questions

Sources

• Coskun, T., et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1, randomised, double-blind, placebo-controlled and active comparator-controlled trial. The Lancet. DOI: 10.1016/S0140-6736(22)02033-5
• Jastreboff, A.M., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972
• Rosenstock, J., et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-comparator-controlled, parallel-group, phase 2 trial conducted in the USA. The Lancet. DOI: 10.1016/S0140-6736(23)01053-X
• Eli Lilly and Company. (2025). Lilly's retatrutide achieved significant weight loss and pain relief in adults with obesity and knee osteoarthritis. Press release.
• ClinicalTrials.gov: NCT04143802, NCT04881760, NCT04867785

Medical Disclaimer

The content on glp3.wiki is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Retatrutide is an investigational drug that has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agency.

Do not use this information to make decisions about your health without consulting a qualified healthcare provider. The clinical trial data cited on this page reflects results from controlled research settings and may not reflect real-world outcomes.

If you are considering weight loss medication, talk to your doctor about currently approved options. For information about enrolling in retatrutide clinical trials, visit ClinicalTrials.gov.

This site is not affiliated with Eli Lilly and Company or any pharmaceutical manufacturer.