Retatrutide

Retatrutide is an investigational triple receptor agonist being studied for weight loss, type 2 diabetes, and other weight-related conditions. In clinical trials, it is given as a once-weekly injection under the skin (subcutaneous injection).

Retatrutide works by targeting the receptors for three hormones: GIP, GLP-1, and glucagon, which are involved in appetite, blood sugar, and metabolism. Because it acts on all three receptors, it has been called a "triple agonist", "triple G" weight-loss medicine, or GLP3.

Retatrutide is related to other incretin-based medicines such as semaglutide and tirzepatide. Semaglutide (Ozempic, Wegovy) acts on the GLP-1 receptor, and tirzepatide (Mounjaro, Zepbound) acts on the GIP and GLP-1 receptors.

Retatrutide acts on three receptors: GIP, GLP-1, and glucagon. Having glucagon receptor activity is what sets retatrutide apart from currently approved medicines, and researchers are studying how this added action affects weight loss and other health outcomes.

Retatrutide is being developed by Eli Lilly and Company.

Important safety notice. Retatrutide is an investigational medicine that has not been approved by the FDA. It is only available to participants in clinical trials and cannot be legally purchased, prescribed or compounded. Any retatrutide product sold outside a clinical trial is not legitimate and may be dangerous to your health.

• GIP = glucose-dependent insulinotropic polypeptide
• GLP-1 = glucagon-like peptide-1
• GCG = glucagon

These are natural hormones. Retatrutide works by activating the receptors these hormones normally act on.

Retatrutide works by activating the GIP, GLP-1, and glucagon receptors, which are involved in appetite, blood sugar, and metabolism.

The GIP and GLP-1 receptors may support weight loss and blood sugar control by:

• increasing insulin release when blood sugar rises
• improving how the body takes up glucose
• increasing feelings of fullness
• slowing digestion

The glucagon (GCG) receptor may add further benefit by:

• increasing the amount of energy the body burns
• increasing the breakdown of body fat
• reducing how much fat is stored

Retatrutide is not FDA-approved, so it has no approved uses. It is being studied in Phase 3 clinical trials for:

• obesity and overweight with weight-related conditions
• type 2 diabetes
• knee osteoarthritis pain
• moderate-to-severe obstructive sleep apnea (OSA)
• chronic low back pain
• cardiovascular and renal (kidney) outcomes
• metabolic dysfunction-associated steatotic liver disease (MASLD)

Results from three Phase 3 weight-loss trials are shown below, each in a different group of adults. All three lasted 80 weeks and compared retatrutide with placebo (a dummy injection). The 12 mg dose, the highest dose studied, gave the greatest average weight loss in every trial.

How much weight people lost depended on who was in the trial. People without diabetes lost the most. Weight loss was lower in people with type 2 diabetes, which is also seen with other weight-loss medicines. The trials enrolled different populations, so the results below show what happened in each trial rather than a direct comparison.

These results show how well retatrutide worked in people who stayed on treatment as planned (the "efficacy estimand"). Results that include everyone who was enrolled, including people who stopped treatment, are usually a little lower.

How well did retatrutide work in people without diabetes?

TRIUMPH-1 (NCT05929066) is a Phase 3, 80-week, randomized, double-blind, placebo-controlled trial of retatrutide. It enrolled 2,339 adults with obesity or overweight with at least one weight-related health problem, who did not have type 2 diabetes. All three doses met the primary and key secondary endpoints.

Standout findings

In patients with obesity or overweight with at least one weight-related health problem, and who did not have type 2 diabetes

• 45.3% of participants on retatrutide 12 mg lost 30% or more of their body weight, a level of weight loss usually associated with bariatric surgery
• 65.3% of participants on 12 mg reached a BMI below 30 at 80 weeks
• In a 104-week extension study of 532 participants with a starting BMI of 35 or higher, those who started on 12 mg and then increased to their highest tolerated dose lost an average of 85.0 lbs (30.3%) of their body weight
• Waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and an inflammatory marker (hsCRP) also improved

How well did retatrutide work in people with type 2 diabetes?

In TRIUMPH-2 (NCT05929079), adults with type 2 diabetes and obesity or overweight lost weight and improved their blood sugar control (A1C) over 80 weeks. The trial enrolled 1,152 participants. Their average starting weight was 234.6 lbs (106.4 kg), their average BMI was 38.2, and their average A1C was 7.7%. The results were published in The Lancet in September 2026.

Standout findings

In patients with type 2 diabetes who had obesity or were overweight

• 59.5% of participants on 12 mg no longer met the BMI criteria for obesity by the end of the trial
• Participants on 12 mg who started with a BMI of 35 or higher lost an average of 60.8 lbs (23.4%)
• 52.0% of participants on 12 mg lost 20% or more of their body weight, compared with 1.5% on placebo
• Up to 79.2% of participants on retatrutide reached an A1C of 6.5% or lower, compared with 26.3% on placebo
• Triglycerides, non-HDL cholesterol, systolic blood pressure, waist circumference and an inflammatory marker (hsCRP) also improved at the 12 mg dose

How well did retatrutide work in people with obesity and heart disease?

In TRIUMPH-3 (NCT05882045), adults with severe obesity (BMI of 35 or higher) and established heart disease, with or without type 2 diabetes, lost weight over 80 weeks. The trial enrolled 1,949 participants with an average starting weight of 245.6 lbs (111.4 kg).

On average, participants on the 12 mg dose also had improvements in several heart-related measures:

• Triglycerides fell by 37.0%
• Non-HDL cholesterol fell by 16.5%
• Systolic blood pressure fell by 9.3 mmHg
• Waist circumference fell by 7.5 inches (19.0 cm)
• An inflammatory marker (hsCRP) fell by 51.2%

An early look at major heart events (major adverse cardiovascular events, or MACE) showed fewer events than expected in both the retatrutide and placebo groups, but the results were not statistically conclusive. A dedicated cardiovascular outcomes trial is still ongoing, so retatrutide has not been shown to reduce heart attacks or strokes.

Retatrutide does not have FDA-approved boxed warnings, contraindications or prescribing information, because it is not an approved medicine. Any discussion of its safety is based only on the clinical trial findings available so far.

Retatrutide's most common side effects in trials were digestive, similar to other medicines that act on GLP-1 receptors. Some effects, such as dysesthesia, have been reported more often than is typical for this class. Full, formally reviewed safety information will only be available if the FDA approves the medicine.

Retatrutide is available only to people enrolled in an active clinical trial who meet that trial's eligibility criteria. It cannot be prescribed, purchased or compounded outside of a trial. People interested in clinical trials can search for active studies on ClinicalTrials.gov.

As with other medicines in this class, retatrutide has not been established as safe during pregnancy or breastfeeding, and clinical trials exclude people who are pregnant.

Retatrutide, semaglutide (Wegovy, Ozempic), tirzepatide (Zepbound, Mounjaro), and orforglipron (Foundayo) all act on receptors for hormones involved in appetite and blood sugar. They differ in how many receptors they act on, how they are taken, and what they are approved for.

Wegovy and Ozempic are available as a once-weekly injection or a once-daily tablet. Foundayo is a once-daily tablet. Zepbound and Mounjaro are once-weekly injections, and retatrutide is being studied as a once-weekly injection.

Retatrutide is the only one that acts on three receptors, and the only one that is not FDA-approved, so it has no approved uses. The approved uses of the other medicines are shown below.

Key takeaways:

• Wegovy, Ozempic and Foundayo act on one receptor, GLP-1.
• Zepbound and Mounjaro act on two receptors, GIP and GLP-1.
• Retatrutide adds a third receptor, glucagon. It has not been compared directly with approved medicines in a completed trial, so how its results compare is not yet known.

See more: How does retatrutide compare to tirzepatide?

No. Retatrutide is available only through clinical trials and cannot be bought in pharmacies or online. Because it is not FDA approved, there is no legal way to obtain it for personal use outside a trial.

Products sold online as "retatrutide" or "retatrutide peptide," including vials marketed for research use only, are not legitimate retatrutide. They are not FDA approved, not regulated for safety, purity or dose, and may be dangerous. Under federal law, retatrutide cannot be used in compounded medicines. See "What is 'retatrutide peptide' being sold online?"

Retatrutide does not have a price. It is still in development and is not an FDA-approved medicine, so no commercial cost has been set. Any pricing will only be announced if the medicine is approved and launched.

There is no confirmed approval or launch date. On July 23, 2026, Lilly announced it plans to submit a Biologics License Application (BLA) to the FDA in the first quarter of 2027. The FDA would then review the application, which can take up to about a year depending on the type of review. A regulatory filing is not an approval, and timelines can change. For details, see Retatrutide FDA Approval Status.

The most common side effects of retatrutide in clinical trials were digestive, including nausea, diarrhea, vomiting and constipation. Decreased appetite was also common. Lilly reported that side effects were generally mild to moderate and most resolved during treatment.

Most participants stayed on retatrutide throughout the trials, but some stopped because of side effects:

• TRIUMPH-1: 4.1% (4 mg), 6.9% (9 mg) and 11.3% (12 mg), compared with 4.9% on placebo
• TRIUMPH-2 (type 2 diabetes): 3.8% (4 mg), 11.6% (9 mg) and 7.7% (12 mg), compared with 4.9% on placebo
• TRIUMPH-3 (obesity and heart disease): 9.8% (9 mg) and 13.5% (12 mg), compared with 4.8% on placebo

Dysesthesia, an unusual or unpleasant skin sensation such as tingling, burning or sensitivity to touch, was reported more often with retatrutide than with placebo. In TRIUMPH-1, it occurred in 5.1%, 12.3% and 12.5% of people taking 4 mg, 9 mg and 12 mg, compared with 0.9% on placebo. Urinary tract infections were also slightly more common with retatrutide in TRIUMPH-2.

The long-term safety of retatrutide has not been established because it is still investigational and has not been approved by the FDA. Its full safety profile, including any long-term effects, is still being studied.

It is also important to know that products sold online as "retatrutide," "retatrutide peptide" or "reta" are not FDA-approved, are not legal to sell for human use, and are not tested for safety, purity or correct dose. Using these products can be dangerous. Anyone considering a weight-loss medicine should speak with a healthcare provider about approved options.

In the TRIUMPH trials, participants taking retatrutide started at 2 mg once weekly and increased their dose in steps every four weeks until they reached their target dose:

Each trial also included a placebo group. TRIUMPH-3 tested only the 9 mg and 12 mg doses.

In TRIUMPH-1, the 4 mg dose led to an average weight loss of 47.2 lbs (19.0%) at 80 weeks. Side effects such as nausea were less common with 4 mg than with higher doses (28.6% with 4 mg compared with 42.4% with 12 mg).

All doses are given as a once-weekly injection under the skin.

For the full development timeline and approval status, see Retatrutide FDA Approval Status.