LY3437943 for Obesity

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

74 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug LY3437943 for obesity?

Research shows that LY3437943, also known as Retatrutide, is effective in reducing body weight and improving blood sugar control in obese mice and people with type 2 diabetes. It works by activating certain receptors in the body that help manage weight and metabolism. ^{1 2 3 4 5}

Is LY3437943 (Retatrutide) safe for humans?

In early studies, LY3437943 (Retatrutide) showed a safety profile similar to other treatments in its class, with no major safety concerns reported. It was tested in humans for weight loss and blood sugar control, and further studies are needed to confirm its safety. ^{1 2 3 4 5}

What makes the drug LY3437943 unique for obesity treatment?

LY3437943, also known as Retatrutide, is unique because it targets three different hormone receptors (GIP, GLP-1, and glucagon) to help manage obesity. This triple action can enhance weight loss by reducing calorie intake and increasing energy expenditure, and it is designed to be taken once a week. ^{1 2 3 4 5}

What is the purpose of this trial?

The main purpose of the study is to look at the effect of the study drug compared to placebo on calorie intake, energy metabolism, and appetite. The study will last up to 6 months and may include up to 20 visits.

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, 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 hepatitis.

Timeline

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

Retatrutide: a triple incretin receptor agonist for obesity management. [2023]

4. 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]

5. United States 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. [2022]