Retatrutide for Weight Loss
Eli Lilly's investigational triple agonist. Not yet FDA approved. In the TRIUMPH-1 Phase 3 trial, the highest dose produced about 28.3% average weight loss over 80 weeks, the strongest results ever published for a weight loss medication.
Reviewed by GlobalGLP1 editorial team • Last reviewed March 2026 • Sources: FDA prescribing information, peer-reviewed clinical trials
Overview
Retatrutide is an investigational once-weekly injection from Eli Lilly that activates three hormone receptors at the same time: GIP, GLP-1, and glucagon. The popular press has started calling drugs in this class "GLP-3" because they target three pathways instead of just one (semaglutide, GLP-1 only) or two (tirzepatide, GIP plus GLP-1). Retatrutide is not yet FDA approved. It is currently going through Phase 3 trials. In the pivotal TRIUMPH-1 trial reported in May 2026, people on the 12 mg dose lost an average of 28.3% of their body weight over 80 weeks, the highest average ever reported for a weight loss drug. Lilly expects to submit retatrutide for FDA review by late 2026, with a potential approval and launch in 2027 or 2028.
How Retatrutide Works
Retatrutide is the first drug to activate three different gut and metabolic hormone receptors at once. GLP-1 reduces appetite and slows digestion (the path Wegovy uses). GIP adds extra metabolic effects and seems to make GLP-1 work better with fewer stomach side effects (this is the second target Mounjaro and Zepbound hit). Glucagon, the third target, is what makes retatrutide different: it nudges the body to burn slightly more energy at rest and to break down fat stores more readily, while the GLP-1 component keeps blood sugar in check (glucagon alone would raise blood sugar). The combined effect is much larger weight loss than single-target or dual-target drugs. Like other GLP-1s, it is taken as a once-weekly injection.
How You Take It
Retatrutide is not yet FDA approved. The only way to access it currently is through enrollment in an active clinical trial. Anything sold online as "retatrutide" outside a trial is not legitimate, may be unsafe, and is illegal.
How Much Weight You Can Lose
In TRIUMPH-1, the pivotal Phase 3 trial in 2,339 adults with obesity and at least one weight-related health condition (but no diabetes), people on the 12 mg dose lost an average of 28.3% of their body weight over 80 weeks. About 45% lost at least 30% of their body weight, a threshold previously seen mostly with bariatric surgery. For a 200-pound person, 28.3% is roughly 57 pounds. An extension subgroup with starting BMI of 35 or higher reached 30.3% average weight loss at 104 weeks. These are the strongest results published to date for any weight loss medication.
Side Effects
Common Side Effects
- Nausea (about 42% of users at the 12 mg dose in TRIUMPH-1, mostly during dose escalation)
- Diarrhea (about 32% of users)
- Constipation (about 26% of users)
- Vomiting (about 25% of users)
- Decreased appetite (common, this is part of how the drug works)
- Indigestion
- Abdominal pain
- Injection site reactions (uncommon, mild redness near the shot)
Rare but Serious
- Pancreatitis (rare)
- Gallbladder disease
- Thyroid C-cell tumors (boxed warning class effect)
- Hypoglycemia (when combined with insulin or sulfonylureas)
- Possible mild increases in heart rate (under study)
- Allergic reactions
Managing side effects: Side effects in TRIUMPH-1 followed the pattern seen with other GLP-1 medications: worst during the first few weeks and around dose increases, then settling. Roughly one in seven participants on the highest dose stopped early due to side effects. Slower dose escalation is being studied as a way to reduce GI side effects.
Retatrutide Cost & Savings (2026)
Savings programs: Retatrutide is not yet on the market. Once approved, Eli Lilly is expected to offer commercial savings programs similar to those for Zepbound and Mounjaro. Clinical trial participants receive the drug at no cost.
Who Should Not Take Retatrutide
- Personal or family history of medullary thyroid carcinoma (MTC) (class effect with all GLP-1s)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Pregnancy
- Active pancreatitis
- Severe gastrointestinal disease
What to Expect, Month by Month
Trial participants report decreased hunger within the first weeks on the 2 mg starting dose.
Steady increase to 4 mg, then 8 mg. Average 5-10% body weight lost during this phase.
Patients on the 12 mg pathway approach 15-20% weight loss.
TRIUMPH-1 patients reached an average 28.3% weight loss at 80 weeks (about 18 months). Some patients in the extension cohort continued to lose weight beyond that point.
Other Medications to Watch
Like other GLP-1 medications, retatrutide combined with insulin or sulfonylureas can cause dangerously low blood sugar. Dose adjustments will be expected.
Retatrutide slows digestion, which can change how oral medications absorb. Final guidance will come with the FDA label.
Special Situations
Pregnant participants were excluded from clinical trials. Retatrutide will carry a pregnancy warning consistent with other GLP-1s.
A separate set of TRIUMPH trials (TRIUMPH-2, TRIUMPH-4) is studying retatrutide in adults with type 2 diabetes. Results so far show strong A1C reduction along with weight loss.
Subgroup analyses are pending. Older adults were included in TRIUMPH-1.
Not yet studied in adolescents.
What Happens If You Stop
A formal discontinuation trial for retatrutide has not been published. Based on what has been seen with semaglutide (STEP-1 extension) and tirzepatide (SURMOUNT-4), most patients regain a meaningful share of lost weight within a year of stopping a GLP-1. There is no current reason to think retatrutide will behave differently.
How to make stopping easier: When the drug is eventually approved, expect the same long-term-use logic as with Wegovy and Zepbound: building durable eating and exercise habits, and considering staying on a low maintenance dose, are likely to be the recommended approach.
Retatrutide FAQs
No, not yet. As of 2026, retatrutide is still in clinical trials. Eli Lilly is expected to submit it to the FDA for review by late 2026. Standard FDA review takes about 10 months, so an approval decision could come in late 2027, with commercial launch most likely in 2027 or 2028.
Right now, the only legitimate way to access retatrutide is by joining an active clinical trial. Trial information is at clinicaltrials.gov. Anything sold online as "retatrutide" is not FDA approved, has unverified purity and dosing, and is illegal to sell or import. We strongly advise against buying it from gray-market sources.
In trials, retatrutide produced larger average weight loss than either Zepbound (about 22.5% in SURMOUNT-1) or Wegovy (about 14.9% in STEP-1). Roughly 45% of people on the highest dose of retatrutide lost at least 30% of their body weight, a threshold previously reserved for bariatric surgery. The trade-off is that we have less long-term safety and durability data on retatrutide than on Zepbound or Wegovy, both of which have been studied for years.
"GLP-3" is shorthand used by some news outlets, not a formal drug class. It refers to triple agonists like retatrutide that hit three hormone receptors (GLP-1, GIP, and glucagon) at once. GLP-1-only drugs like Wegovy and Ozempic target one receptor. Dual GIP/GLP-1 drugs like Zepbound and Mounjaro target two. There is no commercial "GLP-2 weight loss drug" class; the term is mostly used informally to describe dual agonists. See our explainer at /research/what-is-glp-3 for more.
Best estimate: late 2027 or first half of 2028. That timeline assumes Lilly files for FDA review by Q4 2026, the FDA completes its standard review on schedule, and manufacturing scales fast enough to support a real launch. None of those are guaranteed.
In TRIUMPH-1, about 42% of people on the highest 12 mg dose reported nausea, 32% diarrhea, 26% constipation, and 25% vomiting. Roughly 1 in 7 stopped the drug early because of side effects. The pattern (worst during dose increases, easier over time) is similar to Wegovy and Zepbound.
Related Retatrutide resources
Want to try Retatrutide?
Retatrutide is investigational. The only legitimate path to access it today is enrollment in an active clinical trial. Anything sold online is not FDA approved and may be unsafe.
Medical Disclaimer: This guide is for informational purposes only and is not medical advice. All clinical data is sourced from FDA prescribing information and published peer-reviewed trials. Individual results vary. Always consult a qualified healthcare provider before starting, stopping, or switching any medication.