Retatrutide for Obesity

(TRIUMPH-4 Trial)

Recruiting at 80 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

405 Participants Needed

Trial Summary

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.

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 obesity and type 2 diabetes. ^{1 2 3 4 5}

Is Retatrutide safe for humans?

Retatrutide has been studied for its safety in treating obesity and type 2 diabetes, showing promise in managing these conditions. However, detailed information about its side effects and safety profile is still being evaluated in ongoing trials. ^{1 2 3 4 6}

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 typically target only one. This triple action may enhance its effectiveness in reducing body weight and managing blood sugar levels. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial is testing a weekly medication called retatrutide. It aims to help people who are overweight or obese and have knee osteoarthritis. The study will last over a year to see if the medication is safe and effective.

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 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

I have had knee pain for more than 12 weeks and it hurt for over 15 days last month.

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

I have been diagnosed with osteoarthritis according to ACR standards.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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 triple incretin receptor agonist for obesity management. [2023]

3. 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]

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

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

5. 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]

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]