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  1. Medical Information Right
  2. Investigational Drugs Right
  3. Retatrutide-Obesity Right
  4. What is the rationale for the placebo‑controlled design of the TRIUMPH‑Outcomes retatrutide trial?
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Retatrutide-Obesity

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.

What is the rationale for the placebo‑controlled design of the TRIUMPH‑Outcomes retatrutide trial?

TRIUMPH-Outcomes is a phase 3, placebo-controlled, event-driven trial of retatrutide in adults with BMI ≥27 and ASCVD and/or CKD, assessing CV and renal outcomes; at design, no incretin therapies were approved for these indications in this population.

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US_cFAQ_RETA010B_TRIUMPH-OUTCOMES_PLACEBO_DESIGN_WMen-US

Content Overview

Why Is TRIUMPH-Outcomes a Placebo-Controlled Trial Instead of an Active-Comparator Trial?

What is the Retatrutide TRIUMPH-Outcomes Clinical Trial Design?

  • What Are the TRIUMPH-Outcomes Inclusion and Exclusion Criteria?
  • What Are the Key Primary and Secondary Endpoints in the TRIUMPH-Outcomes Trial?

Why Is TRIUMPH-Outcomes a Placebo-Controlled Trial Instead of an Active-Comparator Trial?

When the TRIUMPH-Outcomes trial was designed, no incretin-based therapies were approved by regulatory agencies to reduce cardiovascular risk or prevent the worsening of kidney function in patients with overweight or obesity and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).

Per study protocol, investigators were encouraged to optimize participants' standard of care therapies for CV risk management and/or CKD during the trial, in accordance with local treatment guidelines.1

Back to Content Overview

What is the Retatrutide TRIUMPH-Outcomes Clinical Trial Design?

TRIUMPH-Outcomes is a phase 3, randomized, double-blind, placebo-controlled, event-driven study. The main purpose of this study is to determine if retatrutide can significantly 

  • lower the incidence of serious CV complications, or
  • prevent the worsening of kidney function.2

The trial includes adults with body mass index (BMI) ≥27 kg/m2 and ASCVD and/or CKD.2

Participants are randomized to receive either retatrutide or placebo, administered subcutaneously (SC), with retatrutide doses escalated to a maximum tolerated dose. The study will last for about 5 years.2

What Are the TRIUMPH-Outcomes Inclusion and Exclusion Criteria?

 TRIUMPH-Outcomes Clinical Trial Participation Criteria presents the TRIUMPH-Outcomes participant criteria.

 TRIUMPH-Outcomes Clinical Trial Participation Criteria2

Inclusion Criteria

Exclusion Criteria

  • ≥45 years old
  • BMI ≥27.0 kg/m²
  • Established ASCVD and/or CKD, as evidenced by at least one of the following:
    • coronary artery disease
    • cerebrovascular disease, or
    • peripheral arterial disease
    • CKD defined as
      • eGFRa <45 mL/min/1.73 m² and UACR >30 mg/g
      • eGFRa <60 mL/min/1.73 m² and UACR >100 mg/g, or
      • eGFRa <75 mL/min/1.73 m² and UACR >300 mg/g
  • Participants may be without T2D or with T2D if their HbA1c is ≤10%
  • Type 1 diabetes or any history of diabetic ketoacidosis.
  • Any of the following conditions within 90 days prior to randomization:
    • myocardial infarction
    • acute coronary syndrome
    • stroke, or
    • coronary/peripheral/carotid artery revascularization procedure.
  • Acute decompensated heart failure requiring hospitalization
  • NYHA Class IV heart failure at screening
  • eGFR <20 mL/min/1.73 m² at screening
  • UACR >5000 mg/g at screening
  • Received dialysis within 90 days of randomization
  • Have undergone or are scheduled for a kidney transplant
  • Had or plan to have surgical treatment for obesity
  • History of chronic or acute pancreatitis
  • A family or personal history of medullary thyroid carcinoma, or MEN syndrome type 2
  • Clinically significant gastric emptying abnormality, such as severe gastroparesis, or gastric outlet obstruction

Abbreviations: ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; CKD = chronic kidney disease; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; MEN = multiple endocrine neoplasia; NYHA = New York Heart Association; T2D = type 2 diabetes; UACR = urine albumin-creatinine ratio.

aeGFR is calculated by central lab based on CKD-EPI creatinine-cystatin c equation as determined by central lab.

Back to Content Overview

What Are the Key Primary and Secondary Endpoints in the TRIUMPH-Outcomes Trial?

 TRIUMPH-Outcomes Primary and Secondary Endpoints presents the trial endpoints.

 TRIUMPH-Outcomes Primary and Secondary Endpoints2

Primary Outcome Measuresa

Time to first occurrence of composite endpoints

Composite endpoint includes

  • nonfatal MI
  • nonfatal stroke
  • CV death, or
  • hospitalization or urgent visit due to HF.

Time to first occurrence of composite endpoint of

  • ESKD, defined as the following individual components:
    • persistent eGFR <15 mL/min/1.73 m2 b
    • initiation of dialysis for at least 28 days, or
    • receiving a kidney transplant.
  • ≥40% sustained decline in eGFRc
  • CV death, or
  • renal death.

Secondary Outcome Measuresa

Time to first occurrence of composite endpoint of MACE-3, which includes

  • CV death
  • nonfatal MI, and
  • nonfatal stroke.

Time to first occurrence of composite endpoint of CV death or hospitalization/urgent visit due to HF

Time to occurrence of all-cause death

Time to first occurrence of composite endpoint of ≥40% sustained decline in eGFR, ESRD, or renal death

Percentage change from baseline albuminuria (UACR) in participants with UACR ≥30 mg/g (0.03 mg/mg) at baseline.

Abbreviations: CV = cardiovascular; eGFR = estimated glomerular filtration rate; ESKD = end-stage kidney disease; ESRD = end-stage renal disease; HF = heart failure; MACE = major adverse cardiovascular event; MI = myocardial infarction; UACR = urine albumin-creatinine ratio.

aTimeframe is from randomization to study completion (approximate 248 weeks).

bConfirmed by 2 measurements at least 4 weeks apart at the central laboratory.

cConfirmed by a repeated measure at least 4 weeks after the first result.

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Reference

1Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2The effect of retatrutide once weekly on cardiovascular outcomes and kidney outcomes in adults living with obesity (TRIUMPH-Outcomes). Clinicaltrials.gov identifier: NCT06383390. Updated January 21, 2026. Accessed February 5, 2026. https://clinicaltrials.gov/study/NCT06383390

Date of Last Review: February 03, 2026

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