Retatrutide for Obesity

Recruiting at 1056 trial locations

Overseen By Joseph Soufer

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Type 1 diabetes, Recent heart attack, 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: 27

Duration: 248 weeks

10000 Participants Needed

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 if it can reduce serious heart problems or prevent the progression of kidney disease. It targets adults who are overweight (BMI of 27 or higher) and have heart disease or chronic kidney issues. Participants will receive either retatrutide or a placebo, a harmless substance resembling the treatment. Individuals with conditions like coronary artery disease or chronic kidney disease may qualify for this study. The trial will last about 5 years and includes up to 27 visits to the study doctor. 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. It's best to discuss this with the study doctor to understand how your medications might interact with the trial.

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

Research has shown that retatrutide is safe for people with obesity. In studies, participants lost weight and experienced improved overall health. Most tolerated it well, with common side effects such as nausea or diarrhea, typical for weight-loss treatments. These findings suggest that retatrutide is safe for use in controlled settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Retatrutide is unique because it offers a new approach to weight loss by targeting multiple pathways involved in regulating appetite and energy balance. Unlike current treatments for obesity that primarily focus on a single mechanism, Retatrutide acts on multiple receptors simultaneously, which may enhance its effectiveness in reducing body weight. Researchers are excited because this multi-receptor approach has the potential to lead to greater and more sustained weight loss compared to standard treatments. Additionally, Retatrutide is administered via subcutaneous injection, which could improve patient adherence by potentially offering a more convenient dosing schedule.

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

Research has shown that retatrutide, which participants in this trial may receive, can significantly aid weight loss in people with obesity. One study found that participants lost over 24% of their initial weight after 48 weeks of treatment. Retatrutide also improves how the body converts food into energy. Many participants in these studies reported achieving their weight loss goals. These findings suggest that retatrutide effectively reduces body weight and enhances overall health in people with obesity. ^{1 2 3 4 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 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 with obesity (BMI of 27 or higher) who also have heart disease and/or chronic kidney disease. It's not specified who can't join, but typically those with conditions that could interfere with the study or pose a risk to their health are excluded.

Inclusion Criteria

My HbA1c level is 10% or lower, with or without type 2 diabetes.

A Body Mass Index of ≥27.0 kilograms per meter squared (kg/m^2)

I have heart disease, stroke history, or kidney disease with specific test results.

Exclusion Criteria

Participants have an eGFR <20 mL/min/1.73 m^2 at screening, Have UACR >5000 mg/g at screening, Have received any form of dialysis ≤ 90 days from the date of randomization, Have either undergone a kidney transplant or have a transplant procedure scheduled

Participants have had or plan to have a surgical treatment for obesity, Have a history of chronic or acute pancreatitis, Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome type 2, Have a known clinically significant gastric emptying abnormality, such as severe gastroparesis or gastric outlet obstruction

I haven't had a heart attack, stroke, or heart failure in the last 3 months.

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 administered subcutaneously with up to 27 clinic visits over approximately 248 weeks

248 weeks

Up to 27 visits (in-person)

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 TRIUMPH-OUTCOMES trial is testing if retatrutide, given once weekly, can reduce serious heart complications or slow down kidney function decline in obese individuals compared to a placebo.

How Is the Trial Designed?

Group I: Retatrutide Experimental Treatment 1 Intervention

Participants will receive escalated doses of retatrutide administered subcutaneously (SC) up to a maximum tolerated dose.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo administered SC.

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

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]

Diets of 800 kcal/day lead to significantly greater weight loss compared to weight loss medications, highlighting the importance of dietary changes alongside any pharmacological treatment for obesity.

Orlistat and sibutramine are the only long-term approved medications for obesity, with orlistat also providing additional benefits like lowering LDL cholesterol, while metformin and acarbose are promising options for weight loss in obese type 2 diabetes patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity medications and the treatment of type 2 diabetes. Greenway, F.[2018]

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 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 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]

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]

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

Triple hormone receptor agonist retatrutide for metabolic ... A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively.