Retatrutide for Obesity

(TRIUMPH-4 Trial)

Not currently recruiting at 87 trial locations

Overseen By Stacey Layle

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs

Disqualifiers: Steroid injections, Joint disease, Diabetes, 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

Duration: 73 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called retatrutide to determine its safety and effectiveness for individuals with obesity and knee osteoarthritis, a joint condition causing pain and stiffness. Participants will receive either retatrutide or a placebo (a harmless pill with no active ingredients) once a week for about 77 weeks. It suits those with a BMI of 27 or higher, who have tried but struggled to lose weight, and who have experienced knee pain for more than 12 weeks. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that retatrutide is likely to be safe for humans?

Research has shown that retatrutide is generally well-tolerated by people with obesity. One study found that participants lost over 24% of their starting weight after 48 weeks of treatment. The safety of retatrutide is considered acceptable, meaning it is safe enough based on current research. However, about 2.5% of participants experienced serious side effects, though these were rare.

Further testing of this treatment is underway, indicating that earlier studies deemed it safe enough to continue research. For those considering joining a trial, these findings suggest that while some risks exist, many people have used retatrutide with few problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Retatrutide is unique because it targets obesity using a novel mechanism that combines multiple hormone pathways involved in appetite and weight regulation. Unlike current treatments, which often focus on a single pathway, Retatrutide's multi-pathway approach could potentially lead to more effective and sustained weight loss. Researchers are excited about this treatment because it is administered subcutaneously, which might improve patient adherence compared to oral medications. This innovative approach could offer a promising alternative for those struggling with obesity.

What evidence suggests that retatrutide might be an effective treatment for obesity?

Research has shown that retatrutide helps adults with obesity lose weight. In one study, participants lost over 24% of their starting weight after 48 weeks of treatment. Another study found that it also improved overall metabolic health. Most participants in these studies reached their weight loss goals. This trial will evaluate different doses of retatrutide, which could offer a promising option for managing obesity. ^{1 2 3 6}

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 adults who have been unsuccessful in past dieting efforts, are overweight or obese with a BMI ≥27, and suffer from knee pain due to osteoarthritis. They must not have used weight loss drugs recently, had certain joint procedures within the last 6 months, plan surgical treatments for obesity, have diabetes or other joint diseases besides OA.

Inclusion Criteria

Must have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight

Must have knee X-ray with moderate radiographic changes (Kellgren-Lawrence Grade 2 or 3) per central reading at screening

Body mass index (BMI) must be ≥27 kilogram/kg/m² at screening

Exclusion Criteria

I have had steroid injections in my joints within the last 3 months.

I have had joint injections or procedures in the last 6 months.

I have a joint condition that is not osteoarthritis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive retatrutide or placebo once weekly for the duration of the study

73 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 Retatrutide (LY3437943), given once weekly against a placebo to see if it's safe and effective for those with obesity/overweight and knee osteoarthritis. The trial will monitor participants over approximately 77 weeks.

How Is the Trial Designed?

Group I: Retatrutide Dose 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide SC.

Group II: Retatrutide Dose 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide subcutaneously (SC).

Group III: Placebo Placebo Group 1 Intervention

Participants will receive placebo.

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

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]

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 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]

This study will involve 200 participants with obesity who will first follow a very low-calorie diet for 8 weeks to lose at least 5% of their body weight, followed by a year-long treatment with either liraglutide, exercise, or a combination of both to assess weight loss maintenance.

The primary goal is to evaluate the effectiveness of these interventions in maintaining weight loss and improving immunometabolic health, with results expected to provide insights into effective strategies for long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet. Jensen, SBK., Lundgren, JR., Janus, C., et al.[2023]

In a large study of 5,580 overweight and obese patients, rimonabant (20 mg/day) led to significant weight loss of 6.5 kg and improvements in cardiometabolic risk factors, including waist circumference, HDL cholesterol, and triglycerides after one year of treatment.

While rimonabant was generally well tolerated, it was associated with more gastrointestinal, neurological, and psychiatric adverse events compared to placebo, particularly depressive disorders and anxiety, although serious adverse events were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Van Gaal, L., Pi-Sunyer, X., Després, JP., et al.[2018]

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]

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 Thirty of 36 retatrutide-treated participants had weight reduction as a goal, and 76.7% reported achieving their goal. Conclusion. In this exit ...

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. nature.com nature.com/articles/s41591-024-03018-2

Triple hormone receptor agonist retatrutide for metabolic ... Two participants treated with retatrutide (2.5%) experienced a total of three serious adverse events (Extended Data Table 2). There were no ...

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 ...