An investigational once-weekly GIP, GLP-1 and glucagon triple agonist from Eli Lilly, in late phase 3 for obesity. Not approved.
Also called LY3437943, Reta, triple G, GGG agonist
Retatrutide is a 39-amino-acid peptide that activates three hormone receptors at once: GIP, GLP-1 and glucagon. The first two cut appetite and improve blood sugar, the same way tirzepatide does. The glucagon arm is the new part: glucagon tells the liver to burn fat and raises energy use, which is why the liver fat results stand out. One injection lasts about 6 days.
The phase 3 TRIUMPH program finished its core trials in 2026. In TRIUMPH-1, 2,339 adults with obesity and no diabetes lost an average of 25.0% of body weight over 80 weeks on 12 mg, against 3.9% on placebo (counting everyone randomized; Lilly's efficacy-estimand figure, which estimates the result if everyone had stayed on treatment, is 28.3%). In people with type 2 diabetes (TRIUMPH-2), the average was 18.8%. Knee arthritis pain and sleep apnea events also fell. In a 2024 substudy, 86% of people with fatty liver on 12 mg reached normal liver fat by 24 weeks.
Retatrutide is not approved anywhere. Lilly has said it plans to file with the FDA in the first quarter of 2027. The side effects so far are the usual GI ones plus two that need watching: a dose-related rise in heart rate and dysesthesia (burning or tingling skin) in up to 21% at 12 mg. Vials sold online as research chemicals are unapproved drugs of unknown content, and FDA has sent warning letters to sellers since 2024.
What it binds to, and what happens inside the body after that, step by step.
Retatrutide is most potent at the GIP receptor and somewhat less potent than the native hormones at the GLP-1 and glucagon receptors. GIP and GLP-1 activity lower appetite, raise glucose-dependent insulin and slow stomach emptying. Glucagon activity raises energy expenditure and fat burning in the liver, which may explain why weight and liver fat fall further than with dual agonists. The glucagon effect would raise blood sugar on its own, but the GLP-1 and GIP arms more than offset it.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
Multiple randomized trials, including at least four phase 3 trials with about 6,000 participants combined, show large weight loss (about 19% to 25% at 80 weeks on the treatment-regimen analysis), lower HbA1c in type 2 diabetes, less knee pain and fewer sleep apnea events. What is missing: approval, any trial longer than about 2 years, and outcome data on heart attacks, strokes or death. The cardiovascular signal in TRIUMPH-3 was too small to read either way.
2,339 adults with obesity, no diabetes; subgroups with knee osteoarthritis (574) and sleep apnea (243)
Weight change at 80 weeks was -17.6% (4 mg), -23.7% (9 mg) and -25.0% (12 mg) vs -3.9% on placebo; sleep apnea events fell by about 32 to 34 per hour vs about 10.
Read the study1,152 adults with type 2 diabetes and BMI 27 or higher
Weight change at 80 weeks was -11.9% (4 mg), -16.8% (9 mg) and -18.8% (12 mg) vs -5.1% on placebo; stopping for side effects reached 12% at 9 mg.
Read the study338 adults with obesity or overweight
Weight change at 48 weeks was -24.2% on 12 mg vs -2.1% on placebo; 83% on 12 mg lost at least 15%.
Read the study281 adults with type 2 diabetes
HbA1c fell about 2.0 points on 8 to 12 mg vs no change on placebo at 24 weeks, with dose-dependent weight loss.
Read the study98 adults with obesity and at least 10% liver fat
Liver fat fell 82.4% on 12 mg vs +0.3% on placebo at 24 weeks; 86% on 12 mg reached normal liver fat.
Read the studyAdults with obesity or overweight and knee osteoarthritis
Lilly reported 28.7% average weight loss on 12 mg and 26.4% on 9 mg at 68 weeks vs 2.1% on placebo, and WOMAC knee pain scores fell about 4.5 points from a baseline near 6.
Read the study72 adults with type 2 diabetes
Half-life was about 6 days and placebo-adjusted HbA1c fell up to 1.6 points over 12 weeks.
Read the studyNo preclinical studies are listed as key studies here. The human data above carries the evidence.
These are questions the published research has not answered.
No product containing Retatrutide is approved as a medicine by the FDA.
Phase 3 (TRIUMPH program, Eli Lilly). As of October 2026 no marketing application has been filed; Lilly says it plans to submit to the FDA in the first quarter of 2027 for obesity, knee osteoarthritis pain and obstructive sleep apnea. WADA: not named on the Prohibited List, but as a substance with no government approval for human use it falls under section S0 (non-approved substances), which is prohibited at all times. This is our reading of the S0 rule, not a WADA ruling on retatrutide by name.
How much of Retatrutide is left after a single dose
Simple first-order model from the published half-life. Real clearance varies with dose, route, kidney and liver function and formulation. This is not a dosing schedule.
This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
It is not approved anywhere as of October 2026. Lilly has said it plans to file in the first quarter of 2027, and a standard FDA review then takes about 10 to 12 months.
Lilly's headline numbers (28.3% in TRIUMPH-1, and 30.3% at 104 weeks in a blinded extension limited to people with BMI 35 or higher) use the efficacy estimand at the 12 mg dose, which estimates the result if everyone had stayed on treatment. Counting everyone randomized, the 80-week average was 25.0% on 12 mg in people without diabetes and 18.8% in people with type 2 diabetes.
No independent testing ties those vials to Lilly's molecule, dose or sterility. FDA calls them unapproved new drugs, and FDA adverse event reports have recorded hospitalizations linked to unapproved retatrutide.
Detailed body composition data from phase 3 have not been fully published. There is no human evidence yet that retatrutide spares muscle better than tirzepatide or semaglutide.
Besides the usual GI effects, it causes dysesthesia (burning or tingling skin) in up to about 1 in 5 people on 12 mg in one trial, a dose-related heart rate rise, and more low blood pressure than placebo.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Discussed online as a way to add amylin-driven fullness on top of the triple agonist, by analogy with CagriSema.
EvidenceAnimal data only: a 2026 study in obese male rats reported more weight loss with the combination. No human trial has tested it.
Claimed online to protect muscle during rapid weight loss.
EvidenceNo human or animal study of these combinations exists. Rationale is speculative.
No approved product exists. Trial supply is a ready-to-use solution handled under the sponsor's protocol. Storage claims for research-chemical powders are vendor statements, not tested data.
Not established outside clinical trials.
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