Retatrutide vs Tirzepatide for Obesity

(TRIUMPH-5 Trial)

Recruiting at 68 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs

Disqualifiers: Obesity surgery, Thyroid cancer, Pancreatitis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaluate the efficacy and safety of retatrutide compared to tirzepatide in adults who have obesity. The study will last about 89 weeks.

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.

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

Research shows that Tirzepatide, a drug similar to Retatrutide, is effective for weight loss in people with obesity and type 2 diabetes, helping them lose weight and improve blood sugar levels. This suggests that Retatrutide, which is being compared to Tirzepatide, may also be effective for weight management. ^{1 2 3 4 5}

Is tirzepatide safe for humans?

Tirzepatide has been shown to be generally safe in humans, with the most common side effects being mild to moderate stomach-related issues. These side effects are similar to those seen with other drugs in the same class and usually do not lead to stopping the treatment. ^{1 2 5 6 7}

How is the drug Retatrutide vs Tirzepatide unique for obesity treatment?

Tirzepatide is unique because it acts as a dual agonist for both GLP-1 and GIP receptors, which helps lower blood sugar and reduce appetite, making it potentially more effective for weight loss compared to other treatments that target only GLP-1 receptors. This dual action could offer better results for people with obesity, especially those with type 2 diabetes, compared to existing GLP-1 based therapies. ^{2 3 8 9 10}

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 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

Trial Timeline

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

Treatment Details

Interventions

• Retatrutide (Other)
• Tirzepatide (Other)

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.

Participant Groups

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

Findings from Research

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 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]

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]

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, 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, 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]

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]

References

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

Weight loss efficiency and safety of tirzepatide: A Systematic review. [2023]

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

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

3. United States 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. [2023]

4. England 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. [2023]

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

A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health. [2022]

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

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

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

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. [2023]

8. Switzerland 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? [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. [2023]