Retatrutide for Obesity

(TRIUMPH-1 Trial)

Not currently recruiting at 212 trial locations

Overseen By Sean Wharton

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs, Stimulants, Hypnotics, others

Disqualifiers: Diabetes, Thyroid carcinoma, Pancreatitis, 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: 24

Duration: 80 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a drug called retatrutide for individuals who are overweight or have obesity. It also examines retatrutide's effects on those with knee osteoarthritis or sleep apnea. Participants may receive either retatrutide or a placebo (a substance with no active drug) during the study. Individuals who have struggled to lose weight through dieting and have a high body mass index (BMI) or conditions like high blood pressure or sleep apnea may be suitable candidates for this trial. 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 if you are using certain sleep-related medications or devices, you may need to stop them at least 3 months before screening. If you are on PAP therapy for sleep apnea, you will need to stop using it temporarily for about 7 days before each sleep study visit.

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

Research shows that retatrutide is generally safe for people with obesity. Earlier studies found it to be safe and effective in promoting weight loss and improving overall health. The side effects were mild and expected, meaning they weren't severe or surprising. Participants in these studies experienced manageable side effects, suggesting that retatrutide is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about retatrutide for obesity because it offers a new approach by targeting multiple metabolic pathways. Unlike current treatments such as orlistat, which reduces fat absorption, or GLP-1 agonists like semaglutide, retatrutide is a triple agonist. It acts on GLP-1, GIP, and glucagon receptors, potentially enhancing weight loss and metabolic health more effectively. This multi-target mechanism could lead to improved outcomes and offer hope for individuals who do not respond well to existing treatments.

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

In earlier studies, retatrutide showed promising results for treating obesity. Research indicates that adults with obesity who took retatrutide for 48 weeks lost significant weight, with many losing more than 24% of their starting weight. Another study found that retatrutide not only aided weight loss but also improved overall health. Participants in these studies expressed high satisfaction, with 76.7% reaching their weight loss goals. These findings suggest that retatrutide could effectively treat obesity, offering significant weight loss and health benefits. In this trial, participants will receive different doses of retatrutide or a placebo to further evaluate its effectiveness and safety. ^{1 2 3 5}

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 with obesity or overweight, having a BMI ≥30 kg/m², or ≥27 kg/m² with conditions like hypertension. Participants should have tried and failed to lose weight through dieting, may have knee pain due to osteoarthritis for over 12 weeks, and/or moderate-to-severe obstructive sleep apnea but not on PAP therapy. Exclusions include diabetes patients, those with certain genetic syndromes (MTC or MEN-2), history of pancreatitis, recent significant weight changes (>5kg in 90 days), joint diseases other than OA, prior obesity surgery plans.

Inclusion Criteria

I have been diagnosed with obstructive sleep apnea.

My knee X-ray shows moderate arthritis (Grade 2 or 3).

You have tried and failed to lose weight through dieting at least once before.

Exclusion Criteria

I haven't used certain sleep or pain medications in the last 3 months.

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

I have had pancreatitis.

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 for 80 weeks

80 weeks

Up to 24 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Optional continuation of retatrutide treatment for an additional 24 weeks

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide

Trial Overview The study tests Retatrutide's effectiveness and safety in reducing body weight over approximately 89 weeks compared to a placebo. It includes participants who also suffer from knee osteoarthritis or obstructive sleep apnea. The trial involves up to 24 visits where the intervention's impact on these conditions will be monitored.

How Is the Trial Designed?

Group I: Retatrutide Extension Period Experimental Treatment 1 Intervention

Participants will receive retatrutide after the placebo-controlled 80 week treatment period for an additional 24 weeks.

Group II: Retatrutide Dose 3 Experimental Treatment 1 Intervention

Participants will receive retatrutide SC.

Group III: Retatrutide Dose 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide SC.

Group IV: Retatrutide Dose 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide subcutaneously (SC).

Group V: 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 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 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]

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