Retatrutide for Obesity

(TRIUMPH-6 Trial)

Not currently recruiting at 53 trial locations

Overseen By Alan Kivitz

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs

Disqualifiers: Diabetes, Thyroid cancer, Heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines retatrutide, a treatment designed to help individuals with obesity maintain weight loss. Participants will take retatrutide for 80 weeks, then be randomly assigned to continue with the same dose, switch to a different dose, or switch to a placebo for an additional 36 weeks. The trial aims to assess retatrutide's effectiveness in sustaining weight loss over time. Suitable candidates have obesity and have struggled to lose weight through diet alone. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken weight loss drugs in the 90 days before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that retatrutide is generally safe for people with obesity. In previous research, participants lost a significant amount of weight and experienced improved health outcomes. Safety information indicates that most people did not experience serious side effects. However, any treatment can have side effects, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Retatrutide is unique because it targets multiple pathways involved in weight regulation, potentially offering more comprehensive weight loss effects compared to current options like GLP-1 receptor agonists. Unlike other treatments for obesity, which primarily focus on a single hormone pathway, Retatrutide acts on GLP-1, GIP, and glucagon receptors all at once, aiming to enhance weight loss and metabolic health. Researchers are excited about Retatrutide because it could lead to greater and more sustained weight loss, providing a new hope for individuals struggling with obesity.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that retatrutide can help people with obesity lose a significant amount of weight. In one study, participants lost up to 24% of their starting weight after 48 weeks of treatment. Another study found an average weight loss of 18.7 kg after 24 weeks, which increased to 26.2 kg after 48 weeks. In this trial, participants will receive different dosing regimens of retatrutide, with some transitioning from one dose to another or to a placebo. Retatrutide not only aids in weight loss but also improves overall health. The safety results from these studies have been positive, making retatrutide a promising option for managing weight. ^{1 2 4 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for individuals with obesity who have successfully lost weight. Participants will first undergo an 80-week phase where everyone takes Retatrutide dose 1, followed by a 36-week phase where they'll be randomly assigned to continue with either the same or a different dose of Retatrutide, or switch to a placebo.

Inclusion Criteria

Have obesity and a history of at least one self-reported unsuccessful dietary effort to reduce body weight

Exclusion Criteria

I or my family have a history of MTC or MEN-2.

I have not had a heart attack, stroke, or been hospitalized for heart issues in the last 3 months.

Have a self-reported change in body weight >5 kilograms (kg) (11 pounds) within 90 days before screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Treatment

Participants receive retatrutide dose 1 for 80 weeks

80 weeks

Randomized Double-Blind Treatment

Participants are randomized to receive retatrutide dose 1, retatrutide dose 2, or placebo for 36 weeks

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide

Trial Overview The study tests how well Retatrutide helps maintain weight loss in obese individuals over approximately two and a half years. It involves an initial period where all participants receive the drug, then a randomized phase comparing two doses of Retatrutide against a placebo.

How Is the Trial Designed?

Group I: Retatrutide Dose 1 to Retatrutide Dose 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide dose 1 administered SC for 80 weeks, then retatrutide dose 2 administered SC for an additional 36 weeks

Group II: Retatrutide Dose 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide dose 1 administered subcutaneously (SC) for 116 weeks

Group III: Retatrutide Dose 1 to Placebo Placebo Group 2 Interventions

Participants will receive retatrutide dose 1 administered SC for 80 weeks, then placebo administered SC for an additional 36 weeks

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

In a phase 2 trial involving 281 participants with type 2 diabetes, retatrutide demonstrated significant improvements in glycaemic control, with reductions in HbA1c levels that were greater than placebo and comparable to standard treatments like dulaglutide.

Retatrutide also led to substantial weight loss, with reductions of up to 16.94% at higher doses, while maintaining a safety profile similar to other GLP-1 receptor agonists, with no severe hypoglycaemia or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Rosenstock, J., Frias, J., Jastreboff, AM., et al.[2023]

In a study involving approximately 32,800 users of exenatide, there was a modestly higher incidence of claims for thyroid malignancies compared to users of metformin or glyburide, but this association was not significant when focusing on inpatient claims.

Exenatide use was not linked to an increased risk of benign thyroid neoplasms or pancreatic cancer, suggesting it may be a safe option regarding these specific cancer risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance. Dore, DD., Seeger, JD., Chan, KA.[2021]

Retatrutide, a triple agonist targeting incretin receptors, has shown significant weight loss and reductions in glycated hemoglobin (HbA1c) in phase-2 trials for individuals with type 2 diabetes mellitus (T2DM), as well as substantial weight loss in non-T2DM individuals, although gastrointestinal side effects were noted.

Concerns about cardiovascular safety have emerged due to dose-dependent increases in heart rate and mild to moderate cardiac arrhythmias, highlighting the need for long-term cardiovascular outcome trials to assess its safety in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide: a triple incretin receptor agonist for obesity management. Ray, A.[2023]

In a phase 2 trial with 338 adults, retatrutide significantly reduced body weight over 48 weeks, with the highest dose (12 mg) leading to an average weight loss of 24.2% compared to only 2.1% in the placebo group.

While retatrutide was effective, the most common side effects were gastrointestinal issues, which were generally mild to moderate and could be managed by starting with a lower dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff, AM., Kaplan, LM., Frías, JP., et al.[2023]

In a phase 2 clinical trial, retatrutide demonstrated significant weight loss in participants, with reductions ranging from -7.2% to -18% over 24 weeks, depending on the dosage (1 mg to 12 mg).

While retatrutide shows promise for treating obesity and type 2 diabetes, it also caused an increase in heart rate by up to 6.7 beats per minute, which could be a concern and may counteract some benefits of weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide showing promise in obesity (and type 2 diabetes). Doggrell, SA.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301972

Triple–Hormone-Receptor Agonist Retatrutide for Obesity In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight. (Funded by Eli Lilly; ClinicalTrials.gov number, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12026077/

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and ... Retatrutide demonstrated significant improvements in body weight and metabolic outcomes among adults with obesity and had an appropriate safety profile.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667368125000646

Perceived benefits of treatment for obesity with retatrutide Treatment with retatrutide was associated with a mean weight reduction of up to 17.5% (18.7 kg) at 24 weeks and up to 24.2% (26.2 kg) at 48 ...

4. diabetes.org diabetes.org/newsroom/american-diabetes-association-highlights-novel-agent-retatrutide-results-substantial-weight-reduction-people-with-obesity-type-2-diabetes-during-late-breaking-symposium

San Diego, California Findings demonstrated that participants with obesity lost more than 24% of their starting body weight within 48 weeks of treatment with the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37366315/

Triple-Hormone-Receptor Agonist Retatrutide for Obesity Conclusions: In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight. (Funded by Eli Lilly ...

6. fda.gov fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss

FDA's Concerns with Unapproved GLP-1 Drugs Used for ... FDA has warned companies that have illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that are falsely labeled “for research ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06859268

NCT06859268 | A Study of Retatrutide (LY3437943) in the ... This is a study of retatrutide in participants with obesity. The main purpose is to learn more about how retatrutide maintains body weight loss.