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Retatrutide-Obesity
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What are the preliminary results of retatrutide from TRIUMPH-1 in participants with obesity or overweight without type 2 diabetes?
In TRIUMPH-1, retatrutide 4, 9, and 12 mg met the primary and key secondary endpoints for obesity. With 12 mg dose, mean % change in body weight was -28.3% (-70.3 lb); 45.3% achieved ≥30% weight loss. AEs were consistent with incretin-based therapies.
Content Overview
- What Is the TRIUMPH-1 Study Design in Adults With Overweight or Obesity?
- TRIUMPH-1 Inclusion and Exclusion Criteria
- What Are the Preliminary Efficacy Outcomes of TRIUMPH-1?
- Treatment-Regimen Estimand
- What Are the Preliminary Safety Outcomes of TRIUMPH-1?
- What Are the Future Plans for Retatrutide?
- References
What Is the TRIUMPH-1 Study Design in Adults With Overweight or Obesity?
Retatrutide is an investigational, once-weekly, synthetic molecule with potent agonist action at the:
- glucose-dependent insulinotropic polypeptide (GIP) receptor,
- glucagon-like peptide-1 (GLP-1) receptor, and
- glucagon receptor.1,2
TRIUMPH-1 is a phase 3, randomized, multicenter, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of retatrutide in participants with overweight or obesity without type 2 diabetes. The trial includes 2 basket studies in a subset population with obstructive sleep apnea (OSA) or osteoarthritis (OA) of the knee. Participants were randomized 1:1:1:1 to retatrutide doses (4 mg, 9 mg, or 12 mg) or placebo.1
Participants initiated treatment at a 2 mg dose, which was escalated in 4-week intervals to the randomized target dose; this dose was subsequently maintained throughout the 80-week treatment period.1
Figure 1. TRIUMPH-1 Study Design: A Phase 3 Trial Evaluating the Efficacy and Safety of Retatrutide in Adults with Obesity or Overweight without Type 2 Diabetes 1,4
Figure 1 description: The TRIUMPH-1 study design is a phase 3, randomized, double-blind, placebo-controlled trial evaluating weekly subcutaneous doses of retatrutide (4 mg, 9 mg, 12 mg) compared to placebo over 80 weeks. The trial includes two nested basket studies targeting participants with obstructive sleep apnea and osteoarthritis of the knee, alongside the general weight management cohort. Participants are randomized 1:1:1:1 and receive a fixed dose-escalation regimen with integrated lifestyle counseling.1
Abbreviations: OA = osteoarthritis; OSA = obstructive sleep apnea; PBO = placebo; QW = once weekly; WM = weight management.1
Dose escalation was fixed, and 2 dose reductions were permitted for intolerable gastrointestinal adverse events during the first 20 weeks or for participants who reached a body mass index (BMI) ≤22 kg/m2 or who perceived excessive weight loss.1,4
All participants received individualized lifestyle counseling focusing on:
- Healthy diet rather than caloric restriction, and
- At least 150 minutes of moderate-intensity physical activity per week that includes a strength-training component.1
TRIUMPH-1 Inclusion and Exclusion Criteria
Please refer to Figure 2 for key inclusion and exclusion criteria for TRIUMPH-1.1
Figure 2. TRIUMPH-1 Key Inclusion and Exclusion Criteria1
Figure 2 description: Key inclusion criteria include adults aged 18 or older with at least one failed attempt at dietary weight loss, a BMI of ≥30 kg/m2 or ≥27 kg/m2 with at least one obesity-related comorbidity (dyslipidemia, obstructive sleep apnea, hypertension or cardiovascular disease). Key exclusion criteria include type 1 diabetes or type 2 diabetes, weight change >5 kg within 90 days of screening, secondary causes of obesity, renal impairment, pancreatitis, acute or chronic hepatitis or liver disease, malignancy within 5 years, uncontrolled thyroid disease, medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 family or personal history, elevated calcitonin, acute myocardial infarction, stroke, revascularization, unstable angina, or congestive heart failure hospitalization within 90 days of screening, or New York Heart Association Class IV.1
Abbreviations: AHI = Apnea-Hypoapnea Index; BMI = body mass index; CHF = congestive heart failure; CVD = cardiovascular disease; eGFR = estimated glomerular filtration rate; HTN = hypertension; MEN-2 = multiple endocrine neoplasia syndrome type 2; MI = myocardial infarction; MTC = medullary thyroid carcinoma; NYHA = New York Heart Association; OA = osteoarthritis; OSA = obstructive sleep apnea; PAP = positive airway pressure; T1D = type 1 diabetes; T2D = type 2 diabetes.1
What Are the Preliminary Efficacy Outcomes of TRIUMPH-1?
Two statistical estimands, efficacy and treatment-regimen, were used to evaluate efficacy data from TRIUMPH-1:3
- Efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug or other intercurrent event.
- Treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug or other intercurrent event.
Efficacy estimand results are presented in the text and in Table 1 below.3
In TRIUMPH-1, the primary efficacy endpoint for obesity was met by all doses of retatrutide. At 80 weeks, participants had an average change in body weight of:3
- -19.0% (-47.2 lbs) with retatrutide 4 mg,
- -25.9% (-64.4 lbs) with retatrutide 9 mg,
- -28.3% (-70.3 lbs) with retatrutide 12 mg, and
- -2.2% (-5.5 lbs) with placebo.
In addition, 65.3% of participants taking retatrutide 12 mg achieved a BMI <30 kg/m2, falling under the threshold for obesity at 80 weeks, including 37.5% of those who started with class 3 obesity (BMI ≥40 kg/m2).3
Endpoint |
Retatrutide 4 mg |
Retatrutide 9 mg |
Retatrutide 12 mg |
Placebo |
|---|---|---|---|---|
Primary Efficacy Outcome at 80 Weeks |
||||
Percent change in body weighta |
-19.0 (-21.4 kg; -47.2 lbs) |
-25.9 (-29.2 kg; -64.4 lbs) |
-28.3 (-31.9 kg; -70.3 lbs) |
-2.2 (-2.5 kg; -5.5 lbs) |
Key Secondary Endpoints at 80 Weeks |
||||
Change in waist circumference |
-16.3 cm (-6.4 in) |
-21.8 cm (-8.6 in) |
-24.1 cm (-9.5 in) |
-3.6 cm (-1.4 in) |
Percent of participants achieving ≥25% weight reduction |
27.8 |
52.9 |
62.5 |
2.2 |
Percent of participants achieving ≥30% weight reduction |
15.3 |
37.9 |
45.3 |
0.5 |
Percent of participants achieving ≥35% weight reduction |
5.9 |
20.8 |
27.2 |
0.3 |
Pre-specified Extension at 104 Weeksb |
||||
Percent change in body weight at 104 weeksc |
-27.9 (-33.2 kg; -73.3 lbs) |
-29.5 (-36.6 kg; -80.7 lbs) |
-30.3 (-38.5 kg; -85.0 lbs) |
-19.2 (-22.6 kg; -49.9 lbs) |
Notes: For all participants in the primary analysis, the average baseline weight was 112.7 kg (248.5 lbs) and BMI was 40.0 kg/m2. For the pre-specified extension period, the average baseline weight was 121.7 kg (268.3 lbs) and BMI was 42.8 kg/m2.
a Percent body weight reduction with retatrutide 4 mg was a key secondary endpoint.
b The extension period enrolled 532 participants with BMI ≥35 kg/m2 at baseline who had completed the main 80-week study and tolerated their assigned dose of medication.
c Participants in the trial extension received retatrutide at a maximum tolerated dose of 9 mg or 12 mg.
Treatment-Regimen Estimand
For the treatment-regimen estimand, each dose level of retatrutide led to improvements across the primary and key secondary endpoints, as well as the pre-specified extension. Results are presented in Table 2.3
Endpoint |
Retatrutide 4 mg |
Retatrutide 9 mg |
Retatrutide 12 mg |
Placebo |
|---|---|---|---|---|
Percent change in body weight at 80 weeks |
-17.6 (-19.8 kg; -43.7 lbs) |
-23.7 (-26.7 kg; -58.9 lbs) |
-25.0 (-28.2 kg; -62.1 lbs) |
-3.9 (-4.4 kg; -9.7 lbs) |
Percent change in body weight at 104 weeksa |
-25.7 (-30.6 kg; -67.5 lbs) |
-28.7 (-35.6 kg; -78.4 lbs) |
-29.9 (-38.1 kg; -83.9 lbs) |
-18.9 (-22.3 kg; -49.1 lbs) |
a Participants in the trial extension received retatrutide at a maximum tolerated dose of 9 mg or 12 mg.
What Are the Preliminary Safety Outcomes of TRIUMPH-1?
Reported adverse events were mostly consistent with trials of other incretin-based therapies and are detailed in Table 3.3
Adverse Event |
Retatrutide 4 mg |
Retatrutide 9 mg |
Retatrutide 12 mg |
Placebo |
|---|---|---|---|---|
Nausea |
28.6 |
38.4 |
42.4 |
14.8 |
Diarrhea |
25.2 |
34.1 |
32.0 |
13.5 |
Constipation |
23.8 |
25.9 |
26.1 |
10.9 |
Vomiting |
10.6 |
22.8 |
25.3 |
4.8 |
Upper Respiratory Tract Infection |
14.2 |
12.2 |
13.1 |
11.6 |
Dysesthesiaa |
5.1 |
12.3 |
12.5 |
0.9 |
Urinary Tract Infectiona |
7.5 |
8.8 |
8.4 |
5.3 |
Notes: Values are presented as percentages of participants reporting the adverse event.
a Events of dysesthesia and urinary tract infections were generally mild to moderate, the majority resolved during treatment, and most participants continued taking retatrutide.
Adverse events of interest will be continually monitored across the full TRIUMPH clinical trial program.3
Discontinuation rates due to adverse events were 4.1%, 6.9%, and 11.3% with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 4.9% with placebo.3
What Are the Future Plans for Retatrutide?
Detailed TRIUMPH-1 efficacy and safety data along with other phase 3 retatrutide results will be shared at future medical meetings and in peer-reviewed journals throughout the year.4
Dependent on TRIUMPH phase 3 trials in obesity, knee osteoarthritis pain, and obstructive sleep apnea completion, Eli Lilly and Company plans to submit retatrutide by the end of 2026 for regulatory review.4
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
- Giblin K, Kaplan LM, Somers VK, et al. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes Obes Metab. 2026;28(1):83-93. https://doi.org/10.1111/dom.70209
- Jastreboff AM, Kaplan LM, Frías JP, et al; Retatrutide Phase 2 Obesity Trial Investigators. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389(6):514-526. https://doi.org/10.1056/nejmoa2301972
- Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Press release. Eli Lilly and Company; May 21, 2026. Accessed May 21, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
- Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: May 21, 2026