Retatrutide Phase 3: Up to 28.7 % weight loss in TRIUMPH

Retatrutide is a novel drug from Eli Lilly, injected once a week under the skin. It mimics three natural hormones at the same time - hormones that regulate hunger and blood sugar - which is why it is called a triple agonist (a drug that activates three hormone docking sites in the body at the same time). In its final Phase 3 trials (the last and largest testing phase in patients, before a drug can be submitted for approval to a regulatory agency) it produced the strongest weight reduction ever recorded in a randomized Phase 3 trial (a study in which participants are randomly assigned to either the drug or placebo group - this is considered the gold standard for producing meaningful results) of an incretin-based triple agonist (a drug that simultaneously acts on the three incretin hormones GLP-1, GIP, and glucagon - related to Ozempic, Wegovy, and Mounjaro). Results from December 2025 and May 2026 mark a milestone in obesity research.

What are the specific TRIUMPH trial results?

TRIUMPH-1 (May 2026) enrolled 2,339 participants with obesity or overweight. At 80 weeks, patients on 12 mg weekly retatrutide lost an average of 28.3 % of their body weight (approx. 31.9 kg / 70.3 lbs), those on 9 mg lost 25.9 %, and those on 4 mg lost 19.0 %. The placebo group lost only 2.2 %. Earlier, TRIUMPH-4 (December 2025) showed a 28.7 % weight loss in participants with knee osteoarthritis, alongside a 75.8 % reduction in knee pain (measured by the WOMAC score - a standardized questionnaire doctors use to measure osteoarthritis pain and movement limitations in the knee). More than 1 in 8 patients were completely pain-free by the end of the trial.

What other endpoints were achieved?

Beyond weight loss, retatrutide also produced clear improvements in other pre-defined study goals:

• Prediabetes reversal: 72 % of affected participants normalized their blood sugar status. Prediabetes is the precursor stage of type 2 diabetes: blood sugar is already elevated, but not yet in the diabetic range.
• LDL cholesterol: Reduction of approximately 20 %. LDL is commonly known as the „bad" cholesterol, which promotes deposits in the blood vessels.
• Liver fat: In a Phase 2 extension (a follow-up phase attached to an earlier, smaller study), 93 % of participants on 12 mg achieved normalized liver fat content at 48 weeks.
• Type 2 diabetes (TRANSCEND-T2D-1): HbA1c reduction of 1.7-2.0 %. HbA1c is the long-term blood sugar level and reflects blood sugar control over the past two to three months - the central measurement for people with diabetes. Weight loss was 16.8 % (approx. 16.6 kg) at 40 weeks.

What is the safety profile?

The most common adverse events were gastrointestinal (i.e., stomach and gut complaints such as nausea, vomiting, and diarrhea), typical for GLP-1 agonists. Discontinuation rates due to adverse events were 11.3 % on 12 mg, 6.9 % on 9 mg, and 4.1 % on 4 mg (placebo: 4.9 %). Dysesthesia (unusual skin sensations such as tingling or numbness) occurred in 12.5 % of the 12 mg group, 12.3 % of the 9 mg group, and 5.1 % of the 4 mg group (source: Lilly press release and Phase 2 trial, NEJM 2023). These were generally mild and rarely led to discontinuation, but are explicitly highlighted in expert commentary as a novel, characteristic safety signal of retatrutide.

When can approval be expected?

Retatrutide is not approved by the FDA (U.S. regulatory agency) or the EMA (European regulatory agency). An NDA submission (New Drug Application, the formal application for approval in the U.S.) to the FDA is expected in Q4 2026, with a decision realistically in 2027 or later. Seven additional Phase 3 readouts (i.e., the publication of study results) are expected in 2026, including trials for obstructive sleep apnea (nighttime pauses in breathing caused by narrowed or blocked airways in the throat - very common in people with significant excess weight) and MASLD (metabolic dysfunction-associated steatotic liver disease, i.e., fat buildup in the liver caused by metabolic problems).

Who might benefit?

People who currently live with significant excess weight or type 2 diabetes and who do not lose enough weight with existing GLP-1 medications such as Wegovy or Mounjaro could potentially benefit from retatrutide in the future - provided the trials lead to approval and the drug is well tolerated. Until then, retatrutide remains research only.

For detailed information on the mechanism of action and evidence level, visit the retatrutide peptide page. A comparison with the dual agonist tirzepatide is available on the tirzepatide article.

Not medical advice. This article is for informational purposes only about the current state of clinical research. Retatrutide is not an approved medication and should not be used without medical supervision.