Explore Eli Lilly’s Phase 3 TRIUMPH-2 trial results for retatrutide. Discover data on up to 20.8% weight loss, A1C reductions, and cardiometabolic benefits.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
In adults with obesity or overweight and type 2 diabetes, the investigational triple hormone receptor agonist produced up to 20.8% average weight loss and up to a 1.6% reduction in A1C at 80 weeks.
Eli Lilly and Company has reported detailed results from the Phase 3 TRIUMPH-2 trial evaluating retatrutide, an investigational once-weekly triple hormone receptor agonist, in adults with type 2 diabetes and obesity or overweight. At 80 weeks, all three retatrutide doses (4 mg, 9 mg, and 12 mg) produced substantial reductions in body weight and A1C compared with placebo. The results were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan and simultaneously published in The Lancet.
Triple Receptor Activity Translates into Weight and Glycemic Improvements
Retatrutide is a single molecule that activates the receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. The investigational therapy is being studied as a potential treatment for obesity, overweight, type 2 diabetes, and other metabolic conditions.
TRIUMPH-2 (NCT05929079) was an 80-week, randomized, double-blind, placebo-controlled Phase 3 trial conducted under a basket design. The study included a master trial evaluating obesity and type 2 diabetes and a separate basket trial evaluating moderate-to-severe obstructive sleep apnea. A total of 1,152 participants were randomized in a 1:1:1:1 ratio to receive retatrutide 4 mg, 9 mg, 12 mg, or placebo once weekly. Treatment was initiated at 2 mg once weekly, followed by stepwise dose increases every four weeks until the assigned target dose was reached.
At Week 80, retatrutide produced dose-related reductions in body weight compared with placebo.
Outcome at Week 80 | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
Mean body-weight reduction | 12.7% | 19.1% | 20.8% | 4.0% |
Mean weight loss | 29.8 lb (13.5 kg) | 45.4 lb (20.6 kg) | 49.6 lb (22.5 kg) | 9.3 lb (4.2 kg) |
≥20% body-weight reduction | 24.0% | 45.3% | 52.0% | 1.5% |
Among participants with a baseline BMI of 35 or higher, those receiving retatrutide 12 mg lost an average of 60.8 lb (23.4%) of their body weight. By the end of the study, 59.5% of participants receiving 12 mg no longer met the BMI criteria for obesity.
The glycemic findings also showed reductions in A1C from an average baseline of 7.7%.
Glycemic Outcome at Week 80 | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
A1C reduction | 1.4% | 1.6% | 1.5% | 0.2% |
A1C ≤6.5% | 73.1% | 79.2% | 79.0% | 26.3% |
A1C <5.7% | 28.4% | 40.0% | 39.3% | 4.4% |
These results were reported using Lilly’s efficacy estimand, reflecting the treatment effect assuming participants remained on study intervention through Week 80 without initiating prohibited weight-management treatments.
Cardiometabolic Effects and Safety
The 12 mg dose was also associated with reductions in several cardiovascular risk factors, including triglycerides by 39.5%, non-HDL cholesterol by 19.6%, systolic blood pressure by 10.8 mmHg, waist circumference by 6.7 inches (16.9 cm), and high-sensitivity C-reactive protein (hsCRP) by 58.3%.
The most common adverse events with retatrutide were gastrointestinal.
Adverse Event | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg |
Diarrhea | 27.4% | 33.5% | 33.6% |
Nausea | 13.7% | 20.8% | 28.0% |
Constipation | 14.0% | 16.2% | 16.8% |
Vomiting | 5.5% | 10.2% | 15.7% |
Decreased appetite | 5.8% | 12.3% | 17.1% |
Dysesthesia occurred in 4.5%, 5.6%, and 7.3% of participants receiving 4 mg, 9 mg, and 12 mg, respectively, while urinary tract infections occurred in 3.8%, 6.3%, and 8.0%. These adverse events were generally mild to moderate, and the majority resolved during treatment. Discontinuation due to adverse events occurred in 3.8%, 11.6%, and 7.7% of participants receiving 4 mg, 9 mg, and 12 mg retatrutide, respectively, compared with 4.9% with placebo.
Moving Toward Further Clinical Evaluation
The TRIUMPH-2 findings add Phase 3 evidence to the development of retatrutide, showing simultaneous effects on body weight and glycemic control in adults with obesity or overweight and type 2 diabetes. Lilly plans to submit a Biologics License Application to the U.S. Food and Drug Administration in the first quarter of 2027.
Additional results from the moderate-to-severe obstructive sleep apnea basket trial within TRIUMPH-2 are expected to be presented at a future medical meeting and published in a peer-reviewed journal.
Retatrutide remains an investigational molecule and cannot currently be legally sold or marketed for human use.
Reference
“Lilly’s triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes.” Eli Lilly and Company, September 29, 2026
A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight (TRIUMPH-2), ClinicalTrials.gov ID NCT05929079
Bellido V, le Roux C, Ekinci E et al., Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial, The Lancet, September 29, 2026, https://doi.org/10.1016/S0140-6736(26)01861-1
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.