LY3437943 for Obesity

No longer recruiting at 3 trial locations

Overseen By Michael Rosenbaum

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Disqualifiers: Diabetes, Hepatitis, Depression, others

Compensation: Varies

Number of Visits: 20

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, LY3437943 (Retatrutide), to assess its effects on calorie intake, energy use, and appetite in individuals with obesity. Participants will receive injections of either the experimental drug or a placebo (a harmless substance with no effect) to compare results. The trial seeks individuals with a BMI over 30 who have attempted and struggled to lose weight through dieting. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have started or changed the dose of any medications associated with significant weight gain in the past year, you may not be eligible to participate.

Is there any evidence suggesting that LY3437943 is likely to be safe for humans?

Research has shown that LY3437943, also known as retatrutide, is well-tolerated in studies involving adults with obesity. Participants in these studies lost a significant amount of weight and improved their overall health. The treatment did not cause any unexpected or severe side effects, indicating its safety. Although all treatments can have some side effects, current data suggest that retatrutide is generally safe for people with obesity. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Unlike the standard of care for obesity, which often includes lifestyle changes, medications like orlistat, or GLP-1 receptor agonists such as liraglutide, LY3437943 is unique because it is a novel experimental drug administered subcutaneously. Researchers are excited about LY3437943 because it potentially offers a new mechanism of action targeting pathways involved in regulating appetite and energy balance. This could lead to more effective weight loss solutions for patients struggling with obesity, providing an alternative for those who may not respond well to existing treatments.

What evidence suggests that LY3437943 might be an effective treatment for obesity?

Studies have shown that retatrutide (LY3437943), which participants in this trial may receive, can significantly aid weight loss in adults with obesity. Research indicates that using this treatment for 48 weeks results in substantial weight reduction. Additionally, LY3437943 improves key metabolic health markers, crucial for overall well-being. Early findings also suggest it might alleviate obesity-related issues, such as chronic back pain and other metabolic problems. These results suggest LY3437943 could effectively manage obesity and its related health concerns. ^{1 5 6 7 8}

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 individuals with obesity, defined as having a BMI greater than 30 kg/m2. Participants should have tried at least one diet to lose weight without success. Specific details on who can't join are not provided.

Inclusion Criteria

History of at least 1 self-reported unsuccessful dietary effort to reduce body weight

BMI greater than 30 kg/m2

Exclusion Criteria

I have a history of pancreatitis.

I have a history of thyroid cancer or MEN2 in my family or myself.

I have not started or changed the dose of a medication known to cause significant weight gain in the last 12 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3437943 or placebo to assess effects on calorie intake, energy metabolism, and appetite

16 weeks

Up to 20 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3437943

Trial Overview

The study is testing LY3437943 against a placebo to see its effects on how many calories participants eat, their energy use, and appetite levels. It involves up to 20 visits over a maximum of six months.

How Is the Trial Designed?

Group I: LY3437943 Experimental Treatment 1 Intervention

LY3437943 administered subcutaneously (SC)

Group II: Placebo Placebo Group 1 Intervention

Placebo 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

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]

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]

LY3437943 is a novel triple agonist that targets three receptors related to metabolism, showing promising results in obese mice by reducing body weight and improving blood sugar control.

In a phase 1 study, LY3437943 demonstrated a safety profile similar to existing treatments and supported once-weekly dosing, with weight loss effects lasting up to 43 days after a single dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun, T., Urva, S., Roell, WC., et al.[2022]

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]

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]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2301972

Triple–Hormone-Receptor Agonist Retatrutide for Obesity

In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07035093

NCT07035093 | A Study of Retatrutide (LY3437943) in ...

The main purpose of this study is to evaluate the efficacy and safety of retatrutide in relieving chronic low back pain in participants who have obesity or ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37366315/

Triple-Hormone-Receptor Agonist Retatrutide for Obesity

In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.

4.

trials.lilly.com

trials.lilly.com/en-US/trial/405675

A Study of Retatrutide (LY3437943) in Participants ... - Lilly Trials

The main purpose of this study is to evaluate the efficacy and safety of retatrutide once weekly in participants with obesity and established cardiovascular ...

5.

nature.com

nature.com/articles/s44324-025-00054-5

Incretin triple agonist retatrutide (LY3437943) alleviates ...

RETA reduced body weight, improved metabolic parameters, and attenuated tumor outcomes in obesity-associated pancreatic ductal adenocarcinoma.

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)

7.

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.

8.

trials.lilly.com

trials.lilly.com/en-US/trial/549215

A Study of Retatrutide (LY3437943) Compared to Tirzepatide ...

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