Moderate EvidencePeptide

Retatrutide

The triple agonist

Triple Hormone Receptor Agonist (GLP-1 / GIP / Glucagon)

Last updated: August 2026

Evidence Level: Moderate Evidence

Some human data, strong animal studies, plausible mechanism

Regulatory Status: Not approved anywhere. In phase 3 trials. Eli Lilly has said it plans to file for US approval in the first quarter of 2027.

Retatrutide is an experimental once-weekly injection that activates three hunger and metabolism receptors at once: GLP-1, GIP, and glucagon. In trials it has produced the largest average weight loss ever reported for an obesity drug, up to about 24% at 48 weeks in phase 2 and up to roughly 30% in phase 3. It is not approved or legally available anywhere.

How It Works

Semaglutide hits one receptor. Tirzepatide hits two. Retatrutide hits three, and that third one is the interesting part.

GLP-1 receptor: The same target as semaglutide. Slows how fast your stomach empties and signals fullness to your brain, so you eat less without white-knuckling it.

GIP receptor: The second target tirzepatide added. Works alongside GLP-1 on appetite and on how your fat tissue handles incoming calories. The combination appears to be more effective than GLP-1 alone and, oddly, easier on the stomach.

Glucagon receptor: This is the new one. Glucagon is usually thought of as the hormone that raises blood sugar, which sounds like the opposite of what you want. But it also increases energy expenditure, meaning your body burns more calories at rest, and it pushes the liver to burn stored fat.

So GLP-1 and GIP turn the intake down while glucagon turns the burn up. That two-sided effect is the leading explanation for why retatrutide's numbers run so far ahead of the drugs already on the market.

The tradeoff is that adding glucagon activity is exactly the kind of thing that can surprise you at scale. Glucagon raises blood sugar on its own, so a poorly balanced triple agonist could undo its own metabolic benefit. Trials have watched glycemic markers closely for that reason, and so far the GLP-1 and GIP effects appear to more than compensate.

Evidence by Outcome

Each claim below is rated using a GRADE-aligned five-tier system. Same molecule, different outcomes, different evidence.

Evidence at a glance

How we grade

Weight lossModerate
OtherLow

Want to see how this compares to every other peptide? Browse the full evidence matrix, where every graded claim is grouped by outcome and sorted by certainty.

Weight lossModerate certainty

Produces roughly 24% average body-weight loss over 48 weeks at 12mg weekly, with phase 3 trials reporting up to about 30%.

Population: Adults with obesity (BMI ≥30), or BMI ≥27 with a weight-related condition, without type 2 diabetes

Why this rating

The 48-week phase 2 trial is a well-conducted, peer-reviewed, placebo-controlled RCT with a very large effect size and a clean dose-response. The larger phase 3 results point the same direction and are consistent, but they are so far available only through sponsor press releases and conference presentations, so the full methods and safety tables cannot yet be independently scrutinized. That reporting gap is the reason this sits at moderate rather than high.

GRADE downgrade factors applied

Risk of bias: Methodological flaws in the studies (e.g. lack of blinding, allocation concealment, high attrition).

Supporting studies

Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 TrialRandomized Controlled Trial
New England Journal of Medicine2023n=338
24.2% mean weight reduction at 48 weeks on 12mg versus 2.1% on placebo.
PubMed 37366315 DOI: 10.1056/NEJMoa2301972

Reviewed 2026-08-24· Designing Longevity EditorialHow we grade

OtherLow certainty

Reduces knee osteoarthritis pain in adults with obesity.

Population: Adults with obesity and symptomatic knee osteoarthritis

Why this rating

A single phase 3 trial reported large WOMAC pain reductions, but the result is known only from a sponsor press release, has not been peer-reviewed or replicated, and pain improvement in this population is difficult to separate from the effect of losing roughly a quarter of body weight.

GRADE downgrade factors applied

Risk of bias: Methodological flaws in the studies (e.g. lack of blinding, allocation concealment, high attrition).
Indirectness: Studied population, intervention, comparator, or outcome differs from the question being answered.

Supporting studies

TRIUMPH-4: retatrutide in obesity with knee osteoarthritisRandomized Controlled Trial
Eli Lilly investor release2025
WOMAC knee pain scores reduced by up to about 76% at 68 weeks on the 12mg dose.

Reviewed 2026-08-24· Designing Longevity EditorialHow we grade

Potential Benefits

The largest average weight loss reported for any obesity drug in published trials
Nearly everyone in the phase 2 trial at the two highest doses lost at least 10% of their body weight
Weight loss had still not clearly plateaued at 48 weeks, unusual for this drug class
Improves the usual cardiometabolic markers: waist circumference, blood pressure, lipids, and blood sugar
Phase 3 results reported so far have been positive across five separate trials
A knee osteoarthritis trial reported large reductions in joint pain alongside the weight loss

Risks & Considerations

Not approved. Anything sold as "retatrutide" today is unregulated gray-market material, not the trial drug
Gastrointestinal side effects (nausea, vomiting, diarrhea, constipation) were the most common problem, mostly during dose escalation
The glucagon component means blood sugar effects need monitoring, especially in people with diabetes
Dose-dependent heart rate increases were seen in trials
No long-term safety data. The longest published trials run 48 to 80 weeks
Full phase 3 methods and safety tables are not yet peer-reviewed for most of the program
Rapid weight loss of this magnitude raises real questions about muscle loss that trials are still characterizing

Dosing Information

There is no approved dose, because there is no approved product. The doses below are the ones studied in trials, listed so you can read trial coverage intelligently, not as a protocol to copy.

•Phase 2 studied 1mg, 4mg, 8mg, and 12mg once weekly, with gradual escalation
•Phase 3 TRIUMPH-1 studied 4mg, 9mg, and 12mg once weekly
•All trial doses were reached through slow escalation over several months to limit nausea
•Trial drug is administered as a once-weekly subcutaneous injection
•We are not publishing a self-dosing protocol for an unapproved drug, and you should be suspicious of any site that does

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Practical Tips

1If you want retatrutide, the legitimate route today is a clinical trial. Search ClinicalTrials.gov for the TRIUMPH program
2Gray-market vials labeled "retatrutide" have no verified identity, purity, or dose accuracy, and no one is checking
3If your goal is maximum weight loss from something you can actually get legally, tirzepatide is the current answer
4Watch for the peer-reviewed phase 3 publications. Press-release numbers are usually accurate but never complete
5Approval, if it comes, is unlikely before 2027 based on the company's own stated filing timeline

Key Research

Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial

New England Journal of Medicine, 2023

At 48 weeks, the 12mg group lost an average of 24.2% of body weight versus 2.1% on placebo. Every participant on 8mg or 12mg lost at least 5% of their body weight.

View Study

TRIUMPH-1 phase 3 topline results

Eli Lilly investor release, 2025

All three doses met the primary endpoint over 80 weeks in adults with obesity and at least one weight-related condition, with reported average weight loss up to 30.3%. Full peer-reviewed publication is still pending.

View Study

TRIUMPH-4: retatrutide in obesity with knee osteoarthritis

Eli Lilly investor release, 2025

Reported 28.7% average weight loss at 68 weeks on 12mg, alongside reductions in WOMAC knee pain scores of up to about 76%.

View Study

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Frequently Asked Questions

What is retatrutide?

Retatrutide is an experimental once-weekly injection from Eli Lilly that activates three receptors involved in appetite and metabolism: GLP-1, GIP, and glucagon. It is sometimes called a "triple agonist" or "triple G." In clinical trials it has produced the largest average weight loss ever published for an obesity drug. It is not approved by any regulator and is not legally available.

How much weight do people lose on retatrutide?

In the 48-week phase 2 trial published in the New England Journal of Medicine, the 12mg group lost an average of 24.2% of body weight compared with 2.1% on placebo. Phase 3 results reported by Eli Lilly have been higher still, with TRIUMPH-1 reporting up to 30.3% average loss over 80 weeks. For a 220-pound person, 25% is about 55 pounds.

Is retatrutide better than tirzepatide?

On weight loss alone, the trial numbers are higher. Tirzepatide produced about 21% average loss at 72 weeks in SURMOUNT-1; retatrutide produced about 24% at 48 weeks in phase 2. But these are separate trials with different populations and durations, not a head-to-head comparison, so the gap is suggestive rather than proven. Tirzepatide also has the advantage of actually existing as an approved product with years of real-world safety data.

Can I buy retatrutide?

Not legally, and not as the real thing. Retatrutide is not approved anywhere, so there is no pharmacy supply chain for it. Vials sold online as "retatrutide" come from unregulated suppliers with no verified identity, purity, or dosing accuracy, and no regulator is checking. The only legitimate way to receive retatrutide today is by enrolling in a clinical trial.

When will retatrutide be approved?

Eli Lilly has said it plans to submit retatrutide for US approval in the first quarter of 2027. Standard review timelines would put a possible approval decision in late 2027 or 2028, assuming the submission goes smoothly. Any specific date you see quoted before then is speculation.

What are the side effects of retatrutide?

The most common side effects in trials were gastrointestinal: nausea, vomiting, diarrhea, and constipation, mostly during the dose-escalation period and mostly mild to moderate. Trials also observed dose-dependent increases in heart rate. Because retatrutide activates the glucagon receptor, blood sugar was monitored closely, though the overall glycemic effect in trials was favorable.

Why does adding glucagon help with weight loss?

Glucagon is usually known for raising blood sugar, but it also increases how many calories your body burns at rest and prompts the liver to burn stored fat. GLP-1 and GIP reduce how much you eat, and glucagon increases how much you burn. Attacking both sides of the equation is the leading explanation for retatrutide producing larger weight loss than the two-receptor drugs.

Where to source this

See full directory

Editorial inclusion only, no financial relationship with these providers. See our vetting methodology.

TrimRx

LegitScript-certified compounded GLP-1 telehealth

4.3

Compounded GLP-1Brand-name GLP-1

Strongest compliance posture in our initial GLP-1 cohort. LegitScript-certified at both the platform and pharmacy level, with transparent pricing and no major regulatory issues on record. Worth considering as a default option for users prioritizing cleaner sourcing over absolute lowest price.

$179-$259/mo (compounded sema/tirz)

No financial relationship

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Eden

Vertically-integrated GLP-1 telehealth with notable customer-service caveats

3.6

Compounded GLP-1

Eden has the most ambitious supply-chain story in our cohort, they own the pharmacy that fills your prescription, with a publicized per-lot testing program. The catch is the gap between the marketing and the operational record. BBB shows real complaint patterns around billing and refunds, ConsumerAffairs reinforces those themes, and a class-action investigation is examining whether Eden has been sharing health data with third-party advertisers. We list Eden because the structural advantages are real, but we score the experience-side dimensions honestly. If supply-chain integrity matters more to you than billing predictability, this is a contender. If you want predictable cancellation and refund handling, look elsewhere.

Flat-rate; varies by program tier

No financial relationship

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Ro

Established multi-vertical telehealth with insurance concierge for branded GLP-1

3.6

Brand-name GLP-1Compounded GLP-1

The strongest pick in our cohort for users with commercial insurance, hands down. The insurance concierge is a genuine differentiator: on Wegovy or Zepbound with eligible coverage and a manufacturer savings card, your monthly cost drops to $0-$25, which no all-inclusive cash-pay specialist can match. The catch is the multi-product compounder relationship: the April 2025 FDA finasteride alert reflects on Ro's vendor management broadly, and BBB complaints about membership-vs-medication billing transparency are recurring. Pure cash-pay users on compounded GLP-1 will find better value at TrimRx or Eden.

$45 first month, $145/mo + medication

No financial relationship

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