Retatrutide for Obesity

(TRIUMPH-6 Trial)

Recruiting at 52 trial locations

Overseen By Nagwa Lamaie

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs

Disqualifiers: Diabetes, Thyroid cancer, Heart failure, 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

586 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken weight loss drugs in the 90 days before screening.

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

Retatrutide, which targets specific receptors in the body, has shown promise in managing obesity by helping reduce body weight. It has also been effective in lowering blood sugar levels and body weight in people with type 2 diabetes, suggesting its potential benefits for obesity. ^{1 2 3 4 5}

Is Retatrutide safe for humans?

Retatrutide has been studied for its safety in treating obesity and type 2 diabetes, but detailed information on side effects and safety is still being evaluated in clinical trials. ^{1 2 3 4 6}

How is the drug Retatrutide unique for treating obesity?

Retatrutide is unique because it targets three different receptors involved in metabolism: GLP-1, GIP, and glucagon receptors, which may enhance its effectiveness in reducing weight compared to other treatments that typically target only one receptor. ^{1 2 3 4 7}

What is the purpose of this trial?

This is a study of retatrutide in participants with obesity. The main purpose is to learn more about how retatrutide maintains body weight loss. The study will have two treatment phases: an 80 week lead-in phase in which all participants will take retatrutide dose 1 and a 36 week randomized, double-blinded phase in which participants will either take retatrutide dose 1, retatrutide dose 2, or switch to placebo. Participation in the study will last around 125 weeks.

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 individuals with obesity who have successfully lost weight. Participants will first undergo an 80-week phase where everyone takes Retatrutide dose 1, followed by a 36-week phase where they'll be randomly assigned to continue with either the same or a different dose of Retatrutide, or switch to a placebo.

Inclusion Criteria

Have obesity and a history of at least one self-reported unsuccessful dietary effort to reduce body weight

Exclusion Criteria

I or my family have a history of MTC or MEN-2.

I have not had a heart attack, stroke, or been hospitalized for heart issues in the last 3 months.

Have a self-reported change in body weight >5 kilograms (kg) (11 pounds) within 90 days before screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Treatment

Participants receive retatrutide dose 1 for 80 weeks

80 weeks

Randomized Double-Blind Treatment

Participants are randomized to receive retatrutide dose 1, retatrutide dose 2, or placebo for 36 weeks

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Retatrutide

Trial Overview The study tests how well Retatrutide helps maintain weight loss in obese individuals over approximately two and a half years. It involves an initial period where all participants receive the drug, then a randomized phase comparing two doses of Retatrutide against a placebo.

Participant Groups

Group I: Retatrutide Dose 1 to Retatrutide Dose 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide dose 1 administered SC for 80 weeks, then retatrutide dose 2 administered SC for an additional 36 weeks

Group II: Retatrutide Dose 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide dose 1 administered subcutaneously (SC) for 116 weeks

Group III: Retatrutide Dose 1 to Placebo Placebo Group 2 Interventions

Participants will receive retatrutide dose 1 administered SC for 80 weeks, then placebo administered SC for an additional 36 weeks

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

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 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 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]

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

In a study involving approximately 32,800 users of exenatide, there was a modestly higher incidence of claims for thyroid malignancies compared to users of metformin or glyburide, but this association was not significant when focusing on inpatient claims.

Exenatide use was not linked to an increased risk of benign thyroid neoplasms or pancreatic cancer, suggesting it may be a safe option regarding these specific cancer risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance. Dore, DD., Seeger, JD., Chan, KA.[2021]

References

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

Retatrutide: a triple incretin receptor agonist for obesity management. [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. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Diabesity: therapeutic options. [2022]