Retatrutide vs Tirzepatide for Obesity

(TRIUMPH-5 Trial)

Not currently recruiting at 77 trial locations

Overseen By Awawu Igbinadolor

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs

Disqualifiers: Obesity surgery, Thyroid cancer, Pancreatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 85 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two treatments, retatrutide and tirzepatide (a GIP/GLP-1 receptor agonist), for individuals with obesity. Researchers aim to determine which treatment leads to greater weight loss and is safer over approximately 89 weeks. It suits those who have unsuccessfully tried dieting and have not experienced major weight changes or used weight loss drugs recently. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the development of potentially groundbreaking obesity treatments.

Do I need to stop taking my current medications for the trial?

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

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

A previous study found retatrutide to be generally safe, with most participants tolerating it well, similar to other hormone-stimulating treatments. However, about 2.5% of participants experienced serious side effects, though these were uncommon.

Tirzepatide, another treatment, has been safely used for weight loss. Most people tolerate it well, but some may experience mild stomach issues, such as nausea or diarrhea. Serious side effects are rare but possible.

Both treatments are in advanced testing stages, having already undergone some safety checks. For those considering joining the trial, these findings suggest that both retatrutide and tirzepatide have a reasonable safety level. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Retatrutide is unique because it targets multiple pathways involved in obesity, potentially providing more effective weight loss compared to existing treatments like diet, exercise, and other medications. It acts as a triple agonist, meaning it simultaneously activates receptors for GLP-1, GIP, and glucagon, which together help regulate appetite and energy balance. Researchers are excited about retatrutide because this comprehensive approach could lead to greater and more sustained weight loss than current options. Meanwhile, tirzepatide also shows promise by targeting GLP-1 and GIP receptors, offering another multi-faceted attack on obesity, which might enhance its effectiveness over single-pathway medications.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will compare Retatrutide and Tirzepatide for obesity. Research has shown that Retatrutide can help people with obesity lose significant weight. In one study, over 90% of participants lost at least 10% of their starting weight, and about half lost more than 20%. Another study found weight loss of up to 24% in 48 weeks. Tirzepatide, another treatment option in this trial, has also proven effective for weight loss. Some studies reported that participants lost 20% of their body weight by week 72. Both treatments have shown promise in helping people with obesity lose weight successfully. ^{1 2 3 4 6}

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 who are looking to participate in a study lasting approximately 89 weeks. The specific eligibility criteria have not been provided, but typically participants must meet certain health conditions and agree to follow the study's procedures.

Inclusion Criteria

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

Exclusion Criteria

I have had or am planning to have a procedure or device treatment for obesity.

I have a history of pancreatitis.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either retatrutide or tirzepatide administered subcutaneously

85 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide
• Tirzepatide

Trial Overview The trial is testing the effectiveness and safety of two drugs: Retatrutide (LY3437943) and Tirzepatide (LY3298176). Participants will receive one of these medications to compare their impact on obesity over the course of the study.

How Is the Trial Designed?

Group I: Retatrutide Experimental Treatment 1 Intervention

Participants will receive retatrutide administered subcutaneously (SC)

Group II: Tirzepatide Active Control 1 Intervention

Participants will receive tirzepatide 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

Published Research Related to This Trial

Tirzepatide (Mounjaro™) is a new treatment for type 2 diabetes that acts on both GIP and GLP-1 receptors, showing strong results in lowering blood glucose and promoting weight loss based on evidence from five SURPASS clinical trials.

The safety profile of tirzepatide is similar to that of existing GLP-1 receptor agonists, making it a promising option for early intervention in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug: Tirzepatide (Mounjaro™). Gettman, L.[2023]

Tirzepatide, a novel drug that activates both GLP-1 and GIP receptors, shows glucose-lowering and weight loss effects that are at least as effective as traditional GLP-1 receptor agonists, based on a review of studies leading to its approval.

Current evidence suggests that tirzepatide may be more effective than GLP-1 RAs for weight loss, indicating it could become the preferred treatment option for patients with or without diabetes who want to lose weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. Andraos, J., Muhar, H., Smith, SR.[2023]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, has a safety profile similar to other GLP-1 receptor agonists, but higher doses (10mg and above) are associated with increased risks of hypoglycemia and treatment discontinuation.

In clinical trials involving 9818 patients, higher doses of tirzepatide led to more frequent gastrointestinal side effects like nausea, vomiting, and diarrhea, indicating that these adverse events are dose-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable? Meng, Z., Yang, M., Wen, H., et al.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

Tirzepatide, a novel incretin coagonist approved for type 2 diabetes, targets both GLP-1 and GIP receptors, potentially addressing defects in the incretin hormone system that contribute to diabetes.

Phase 2 and 3 trials indicate that tirzepatide effectively lowers hemoglobin A1c and promotes weight loss, with a safety profile showing mostly mild gastrointestinal side effects and a low risk of treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health. Bucheit, J., Ayers, J., Pamulapati, L., et al.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Tirzepatide, a novel GLP-1 receptor agonist, has been shown to significantly reduce A1C levels and body weight in patients with type 2 diabetes compared to placebo and other active treatments.

The safety profile of tirzepatide is similar to other GLP-1 receptor agonists, with the most common side effects being mild to moderate gastrointestinal issues, and it does not increase the risk of hypoglycemia, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. Kushner, P., Anderson, JE., Simon, J., et al.[2023]

Tirzepatide significantly improved blood glucose levels and reduced body weight in type 2 diabetes patients compared to dulaglutide over a 52-week period.

After stopping tirzepatide, patients experienced a rapid increase in blood glucose levels and weight regain, indicating the need for ongoing treatment or careful monitoring after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on Hemoglobin A1c (HbA1c) and Body Weight After Discontinuation of Tirzepatide, a Novel Glucose-Dependent Insulinotropic Peptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist: A Single-Center Case Series Study. Kubota, M., Yamamoto, K., Yoshiyama, S.[2023]

Tirzepatide, a dual GLP-1/GIP receptor co-agonist, has been shown to significantly reduce glycosylated hemoglobin levels (1.87% to 3.02%) and body weight (5.4 to 12.9 kg) in people with type 2 diabetes over treatment periods of up to 104 weeks, demonstrating its efficacy compared to placebo and other diabetes medications.

In individuals without diabetes, tirzepatide also led to substantial weight loss (16.5% to 22.4%) over 72 weeks, indicating its potential for obesity management as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Sinha, R., Papamargaritis, D., Sargeant, JA., et al.[2023]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301972

Triple–Hormone-Receptor Agonist Retatrutide for Obesity With the 12-mg dose of retatrutide, more than 9 of 10 participants lost 10% or more of their baseline weight, nearly two thirds lost 20% or more, nearly half ...

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. 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.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2667368125000646

Perceived benefits of treatment for obesity with retatrutide Treatment with retatrutide was associated with a mean weight reduction of up to 17.5% (18.7 kg) at 24 weeks and up to 24.2% (26.2 kg) at 48 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05929066

NCT05929066 | A Study of Retatrutide (LY3437943) in ... 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)