Retatrutide for Obesity

Recruiting at 926 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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to determine if retatrutide can significantly lower the incidence of serious heart-related complications or prevent the worsening of kidney function. The trial will enroll adults with body mass index 27 kg/m\^2 or higher and Atherosclerotic Cardiovascular Disease and/or chronic kidney disease. The study will last for about 5 years. Participants will have up to 27 clinic visits with the study doctor.

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 Retatrutide safe for humans?

Retatrutide has been studied for obesity and type 2 diabetes, showing promise in managing these conditions. However, its safety profile, including side effects, is still being evaluated in clinical trials. ^{1 2 3 4 5}

How is the drug Retatrutide unique in treating obesity?

Retatrutide is unique because it targets three different hormone receptors (GLP-1, GIP, and glucagon), which is different from most obesity treatments that usually target only one. This triple action may enhance its effectiveness in reducing body weight and managing type 2 diabetes. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Retatrutide for obesity?

Research shows that Retatrutide, which targets specific receptors involved in metabolism, has shown promise in reducing body weight and managing obesity. It has also demonstrated effectiveness in lowering blood sugar levels in people with type 2 diabetes, which is often linked to obesity. ^{1 2 3 4 7}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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 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]

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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. England 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. [2023]

6. United States 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. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

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