Retatrutide has now reported topline results from five Phase 3 trials, and every one met its primary endpoint. Eli Lilly plans to submit the triple GIP, GLP-1 and glucagon receptor agonist for US approval in the first quarter of 2027. This post puts all five trials side by side, compares them with the Phase 2 data, and covers what is still to come.
This article summarises published clinical trial announcements for research and educational purposes. Retatrutide is an investigational compound with no marketing authorisation from any regulatory agency. Torsena supplies it for in-vitro and ex-vivo laboratory research only.
Retatrutide Phase 3 results at a glance
| Trial | Population | Duration | Headline result (highest dose arm) | Reported |
|---|---|---|---|---|
| TRIUMPH-4 | Obesity or overweight with knee osteoarthritis | 68 weeks | 28.7% mean weight reduction, reduced knee pain | Dec 2025 |
| TRANSCEND-T2D-1 | Type 2 diabetes | 40 weeks | A1C down 1.7 to 2.0 points across doses, 16.8% weight reduction | Mar 2026 |
| TRIUMPH-1 | Obesity or overweight, no diabetes | 80 weeks | 28.3% mean weight reduction (30.3% at 104 weeks in extension) | May 2026 |
| TRIUMPH-2 | Obesity or overweight with type 2 diabetes | Not yet detailed | Primary endpoint met, improvements in weight and A1C | Jul 2026 |
| TRIUMPH-3 | Severe obesity with established cardiovascular disease | 80 weeks | Up to 22.6% mean weight reduction | Jul 2026 |
TRIUMPH-4: knee osteoarthritis
TRIUMPH-4 was the first Phase 3 readout, in December 2025. It randomised 445 adults with obesity or overweight and knee osteoarthritis, without diabetes, to one of the two highest trial doses or placebo for 68 weeks. Both doses met all primary and key secondary endpoints, with mean weight reduction of 28.7% in the highest dose arm and significant reductions in knee pain scores.
TRANSCEND-T2D-1: type 2 diabetes
TRANSCEND-T2D-1 enrolled 537 adults with type 2 diabetes not controlled by diet and exercise alone, with an average diabetes duration of 2.5 years. Over 40 weeks, A1C fell by 1.7 to 2.0 percentage points across the three dose arms, against 0.8 on placebo. Mean weight reduction reached 16.8% in the highest dose arm, and participants were still losing weight at week 40. Discontinuation due to adverse events ranged from 2.2% to 5.1% across doses, against 0% on placebo.
TRIUMPH-1: obesity without diabetes
TRIUMPH-1 is the pivotal obesity trial and the largest in the program. Over 80 weeks, mean weight reduction was 19.0%, 25.9% and 28.3% across the three dose arms, against 2.2% on placebo. In the highest dose arm, 45.3% of participants reached a reduction of 30% or more. Participants with a baseline BMI of 35 or higher who continued into a study extension kept losing weight, reaching a mean reduction of 30.3% at 104 weeks. The trial also reported improvements in knee osteoarthritis pain and obstructive sleep apnea.
Gastrointestinal events were the most common adverse events. Nausea occurred in 28.6% to 42.4% of participants across dose arms, against 14.8% on placebo. Discontinuation due to adverse events ranged from 4.1% to 11.3%, against 4.9% on placebo.
Detailed TRIUMPH-1 and TRANSCEND-T2D-1 results were presented at the American Diabetes Association Scientific Sessions on 6 June 2026.
TRIUMPH-2 and TRIUMPH-3: diabetes and cardiovascular disease
Lilly announced both trials together in July 2026. TRIUMPH-2, in adults with obesity or overweight and type 2 diabetes, met its primary endpoint with improvements in both weight and A1C. TRIUMPH-3, in adults with severe obesity and established cardiovascular disease, reported mean weight reduction of up to 22.6% at 80 weeks. Lilly has said detailed results for both will be presented at medical meetings and submitted to peer-reviewed journals.
How Phase 3 compares with Phase 2
The Phase 2 obesity trial published in the New England Journal of Medicine in 2023 reported mean weight reduction of 24.2% at 48 weeks in the highest dose arm. TRIUMPH-1 ran nearly twice as long and reported 28.3% at 80 weeks, then 30.3% at 104 weeks in its extension. The Phase 3 data therefore confirms the Phase 2 signal in a much larger population and shows the effect continuing well beyond the Phase 2 endpoint.
Why the glucagon receptor matters
Retatrutide’s results are usually attributed to its third target. Tirzepatide acts at GIP and GLP-1 receptors, and semaglutide at GLP-1 only. Retatrutide adds glucagon receptor agonism, which preclinical research links to increased energy expenditure and hepatic fat oxidation. Its reported potency is highest at the GIP receptor (human EC50 0.0643 nM), followed by GLP-1 (0.775 nM) and glucagon (5.79 nM). Full receptor and physicochemical data are on our retatrutide research peptide page.
Frequently asked questions
When will retatrutide be approved?
It has not been approved anywhere. Lilly has said it is completing the chemistry, manufacturing and controls package required for a Biologics License Application and plans to submit to the FDA in Q1 2027. Approval would only follow the FDA’s review of that application.
How many Phase 3 trials has retatrutide completed?
As of September 2026, Lilly has reported topline results from five Phase 3 trials: TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, TRIUMPH-4 and TRANSCEND-T2D-1. All five met their primary endpoints.
Which retatrutide trials are still running?
TRANSCEND-T2D-2, comparing retatrutide with semaglutide in type 2 diabetes, and TRANSCEND-T2D-3, in type 2 diabetes with renal impairment, have estimated completion dates in late 2026 and early 2027. TRIUMPH-Outcomes, the long-term cardiovascular and kidney outcomes trial, is estimated to complete in 2029.
How does retatrutide differ from tirzepatide?
Both are 39-amino-acid peptides built on a GIP backbone. Retatrutide adds activity at the glucagon receptor, giving it three receptor targets instead of two.
What to watch next
The next milestones are full peer-reviewed publication of the TRIUMPH results, the remaining TRANSCEND readouts, and the BLA submission. We will update this post as new data is published.
References
Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. N Engl J Med. 2023;389(6):514-526.
Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss. Cell Metab. 2022;34(9):1234-1247.
Eli Lilly and Company. TRIUMPH-4 topline results, 11 December 2025.
Eli Lilly and Company. TRANSCEND-T2D-1 topline results, 19 March 2026.
Eli Lilly and Company. TRIUMPH-1 topline results, 21 May 2026.
Eli Lilly and Company. TRIUMPH-2 and TRIUMPH-3 topline results, 23 July 2026.
ClinicalTrials.gov: NCT05929066 (TRIUMPH-1), NCT05931367 (TRIUMPH-4), NCT06260722 (TRANSCEND-T2D-2), NCT06297603 (TRANSCEND-T2D-3), NCT06383390 (TRIUMPH-Outcomes).
Related: Retatrutide research peptide specifications · Tirzepatide research peptide