An experimental once-weekly injection that switches on three gut and pancreas hormone receptors at once: GLP-1, GIP, and glucagon. In mid-stage trials it produced some of the largest weight losses ever recorded for a drug, and late-stage trials in obesity, diabetes, sleep apnea, knee arthritis, and heart and kidney disease are under way. It is not approved anywhere.
Retatrutide is a single peptide that activates three hormone receptors: GLP-1, GIP, and glucagon. The GLP-1 and GIP arms act on the pancreas and brain to improve glucose control, lower appetite, and slow stomach emptying. The glucagon arm adds something the approved incretin drugs lack, since it raises energy expenditure and pushes the liver to burn fat. In obese mice, that extra glucagon effect added to the weight loss that came from eating less.
Injected once a week (1/7)
Retatrutide is injected once a week, starting at 2 mg and stepping up.
Its pharmacokinetics support once-weekly dosing, and in the first human study a single dose kept weight lower for 43 days afterward. Because stomach slowing is strongest after the first doses, treatment starts low and climbs, and a starting dose of 2 mg caused fewer stomach effects than 4 mg. Heart rate rose with dose, peaking at 24 weeks and easing afterward. In people with type 2 diabetes, the 8 mg and 12 mg doses lowered HbA1c by about 2 percentage points, more than the approved GLP-1 drug dulaglutide.
Retatrutide is being studied as a once-weekly injection for obesity, type 2 diabetes, and the fatty liver disease that often accompanies them. In a phase 2 trial of 338 adults with obesity, people on the 12 mg dose lost 24.2% of their body weight over 48 weeks, against 2.1% on placebo. A companion study in 98 participants with fatty liver disease saw liver fat fall by 81.4% and 82.4% on the two higher doses. Phase 3 trials with over 5800 participants are now testing it for weight loss and for two complications of obesity, obstructive sleep apnea and knee osteoarthritis.
Eli Lilly's trial drug is the only retatrutide that has been tested in people, and no regulator has approved it. The FDA states that retatrutide cannot be used in compounding under federal law and has warned telehealth companies and ingredient suppliers that market it, while regulators in Australia and Canada list it among unapproved injectable peptides sold online. Trial participants receive it alongside a healthy diet and physical activity, with the dose stepped up slowly. Vials sold on the internet or by compounders have no verified identity, purity, or dose, and nothing shows they match the studied product.
Human evidence comes from phase 1 and phase 2 trials run by the manufacturer. The obesity trial randomized 338 adults for 48 weeks, the diabetes trial randomized 281 adults against placebo and dulaglutide, and the liver substudy measured liver fat by imaging in 98 people. All three showed large, dose-dependent effects on weight, blood sugar, or liver fat. None was designed to show whether the drug prevents heart attacks, strokes, or kidney failure.
The biggest unknowns are whether those benefits hold up at scale and over years, which the TRIUMPH phase 3 program and a dedicated cardiovascular and kidney outcomes trial are now testing. Whether weight stays off after stopping and whether the glucagon arm carries risks of its own are open questions. No peer-reviewed phase 3 results had been published when the TRIUMPH design paper appeared in 2026. Nothing is known about the contents or effects of retatrutide sold outside clinical trials.
Nausea, diarrhea, vomiting, and constipation are what trial participants report most, affecting 35% of people on retatrutide against 13% on placebo in the diabetes trial and rising with dose. They were mostly mild to moderate and were eased by starting at a lower dose. Heart rate increased in a dose-dependent way, peaking at 24 weeks before easing, and the safety profile so far matches that of GLP-1 and GIP/GLP-1 drugs. There were no severe hypoglycemia episodes or deaths in the diabetes trial, and nothing is known about the safety of products bought outside trials.
This compound is still in clinical trials. No regulator has approved it for any use.
Retatrutide is an investigational drug with no approval from the FDA or any other regulator. The FDA says it cannot be used in compounding under federal law, has not been found safe and effective for any condition, and has warned telehealth companies, ingredient distributors, and outsourcing facilities that sell it. Australia's TGA and Health Canada both name retatrutide among unapproved injectable peptide products promoted online. The only legitimate access is through a clinical trial.