Retatrutide for Obesity

(TRIUMPH-1 Trial)

Recruiting at 200 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

2300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of retatrutide in participants who have obesity or overweight (J1I-MC-GZBJ master protocol) including subsets of participants who have knee osteoarthritis (OA) (J1I-MC-GOA1) or who have obstructive sleep apnea (OSA) (J1I-MC-GSA1). This study will last about 89 weeks and will include up to 24 visits. Addendum (2) is optional and available to approximately 500 participants to continue treatment with retatrutide for up to an additional 24 weeks.

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.

What safety data exists for Retatrutide in humans?

Retatrutide has been studied for its safety in treating obesity and type 2 diabetes. It acts on multiple hormone receptors and has been evaluated in phase 1 and phase 2 trials, which are early stages of clinical research that assess safety and side effects in humans. ^{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—simultaneously, 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 blood sugar levels. ^{1 2 3 4 6}

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

Research shows that Retatrutide, which targets specific receptors in the body, has been effective in reducing body weight and managing blood sugar levels in people with type 2 diabetes, suggesting it may also help with obesity. ^{1 2 3 4 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 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 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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

Endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus. [2018]